Генетичне консультування, допологова діагностика та клінічні варіанти перебігу муковісцидозу залежно від генотипу: Автореф. дис… канд. мед. наук / Л

OE?A?INUeEEE IAOEIAEE A?A??I?*IEE OeAIO? IIC OE?A?IE

IEOAEEAOeUe Ethaeieea Iao??aia

OAeE.616.37-053.1-0.73.4-8:575.113

AAIAOE*IA EIINOEUeOOAAIIss, AeIIIEIAIAA

Ae?AAIINOEEA OA EE?I?*I? AA??AIOE IA?AA?AO

IOEIA?NOeEAeICO CAEAAEII A?Ae AAIIOEIO

03.00.15 — aaiaoeea

Aaoi?aoa?ao aeena?oaoe??

ia caeiaoooy iaoeiaiai nooiaiy

eaiaeeaeaoa iaaee/ieo iaoe

Eeaa 1999

Aeena?oaoe??th ? ?oeiien.

?iaioo aeeiiaii a ?inoeooo? iaae?ao???, aeooa?noaa oa a?iaeieia?? AII
Oe?a?ie.

Iaoeiaee ea??aiee: aeieoi? iaaee/ieo iaoe, i?ioani?

Ieeeinueea Ia??y Aiae???aia

?inoeooo aenia?eiaioaeueii? ?aae?ieia?? Iaoeiaiai oeaio?o ?aae?aoe?eii?
iaaeeoeeie AII Oe?a?ie, caa?aeoaa/ea eaai?aoi???.

Io?oe?ei? iiiiaioe:

aeieoi? iaaee/ieo iaoe, i?ioani? A?a/ai?ia Ieaia sse?aia, Oa?e?anueea
iaaee/ia aeaaeai?y i?neyaeeieiiii? i?aeaioiaee IIC Oe?a?ie, caa?aeoaa/ea
eaoaae?e;

aeieoi? iaaee/ieo iaoe Oei/aiei Ieueaa ?aai?aia, Oe?a?inueeee iaoeiaee
oeaio? iaaee/ii? aaiaoeee IIC ? IAI Oe?a?ie, caa?aeoaa/ea eaai?aoi???.

I?ia?aeia onoaiiaa

Euea?anueeee iaoeiai-aeine?aeiee ?inoeooo niaaeeiai? iaoieia?? IIC
Oe?a?ie, a?aeae?eaiiy ai?aeai?ieia?? a?iaeaeaii? ? niaaeeiai? iaoieia??,
i. Euea?a.

Caoeno aeena?oaoe?? a?aeaoaeaoueny » 29 » aeiaoiy 1999 ?ieo i 10-00
aiaeei? ia can?aeaii? niaoe?ae?ciaaii? a/aii? ?aaee Ae26.604.01. a
Oe?a?inueeiio iaoeiaiio a?a??i?/iiio oeaio?? IIC Oe?a?ie (253660,
Ee?a-94,aoe. Iiioae?aiea, 50).

C aeena?oaoe??th iiaeia iciaeiieoeny o a?ae?ioaoe? Oe?a?inueeiai
iaoeiaiai a?a??i?/iiai oeaio?o IIC Oe?a?ie (i. Ee?a, aoe. Iiioae?aiea,
50).

Aaoi?aoa?ao ?ic?neaii » 22 » aa?aniy 1999 ?.

A/aiee nae?aoa?

niaoe?ae?ciaaii? a/aii? ?aaee Naeaciueia A.TH.

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE

Aeooaeuei?noue i?iaeaie

Aaiaoe/i? i?aeoiaee o oea?ei? iieiioaiiy caei?ia’y ianaeaiiy noathoue
aeaaeaei iioe?aiioeie. Iia? aaiaoe/i? oaoiieia?? oa iaoiaee ae?aaiinoeee
coiiaeththoue iaiao?aei?noue ia?aaeyaeo e oaeineiiaeaiiy a?aeiieo oi?i
i?io?eaeoeee, e?eoaaiiy ? ?aaa?e?oaoe?? niaaeeiaeo caoai?thaaiue.

Ioeiainoeeaeic (IA) — aooiniiii-?aoeaneaia niaaeeiaa caoai?thaaiiy, yea
coiiaeaii iooaoe??th aaia o?ainiaia?aiiiai ?aaoeyoi?iiai a?eea oa
oa?aeoa?eco?oueny o?aaeaiiyi aecie?eiieo caeic aeeoo?ai aaaeeeaeo
i?aai?a, ?aiiueith iai?oanoaoe??th, oyaeeei ia?aa?aii ? aenieith
eaoaeuei?noth. Iioe?ai?noue eiai a Oe?a?i? noaiiaeoue 1:2200
iiaiia?iaeaeaieo [A.ss. ??ciee oa ?io?, 1994].

IA ia?aaaaeii anioe?th?oueny c iaoieia??th eaaaiue, i?ioa a?i yaey?
niaith nenoaiia caoai?thaaiiy c o?aaeaiiyi ianaiia?aae
oeoieiai-eeoeiaiai o?aeoo, a caiaeii — na?oey oa ?ioeo aeeoo?ai
aaaeeeaeo i?aai?a. Oea caoai?thaaiiy neiae ?icaeyaeaoe ye aaaaoia?aiio
ee?i?/io i?iaeaio, ui i?eaa?oa? oaaao iaae?ao??a, aaiaoee?a ? oao?aoe?a
iieaeoey?ii? a?ieia??.

Aaaeeeaei aeinyaiaiiyi o aea/aii? IA ? ea?ooaaiiy aaia o?ainiaia?aiiiai
a?eea (O?AI) o 1989 ?ioe?, ui aeicaieeei ?ic?iaeoe iaoiaee iieaeoey?ii?
ae?aaiinoeee aeaiiai caoai?thaaiiy [J. Riordan et al,1989; J. Rommes et
al, 1989]. Ia nueiaiaeii aeyaeaii iiiaae 750 iooaoe?e oeueiai aaia
[ECCACF, 1997], aea iaeiioe?aiiooth a a?eueoino? ianoaaeaieo iiioeyoe?e
? “iaaei?ia” iooaoe?y delF508 [B.Kerem et al,1989; L.Tsui,1995]. *anoioa
?o aa??th? — ?c i?i?iaeueiei cia/aiiyi o Oo?a//ei? (27%) ? iaeneiaeueiei
o Aeai?? (88%) [I.Handrieser et al, 1990; M.Schwartz et al, 1990;
H.Johansen,1991].

A?aee?eooy aaia IA aoei iia’ycaia c aaeeeeie iaae?yie ia oaeaeeee
i?aeoe/iee ?acoeueoao, aea aeyaeeiny, ui oey aaaeeeaa iiae?y — eeoa
ii/aoie aeiaaiai ? aaaeeiai oeyoo aei iieaaoaiiy aeie? ethaeae, eio?i
no?aaeaeathoue ia ioeia?noeeaeic. Ianooiiei aoaiii, ia iaio cia/iei,
aiiae naia a?aee?eooy aaia, ? inieneaiiy i?ioean?a, yei, a?aeaoaath/enue
a i?aai?ci? iin?y aai?a, ni?e/eiythoue caoai?thaaiiy.

Aaaaoi yei aaoi?e aeacothoue ia ae?aciee ee?i?/iee iie?ii?o?ci ?
??ciiia?ooy aa??aio?a ia?aa?ao IA: a?ae aaaeeeo oi?i ?c eaoaeueiei
eiioeai o ?aiiueiio aeeoeinoa? aei iaeaea oeieeiaeoi? a?aenooiino?
neiioiiaoeee, ca aeiyoeii i?aeaeuaii? eiioeaio?aoe?? aeaeo?ie?o?a iioo
[A.ss.??ciee oa ?i.,1994, I.I.Eai?aiia oa ?i.,1995, A.A. Iaaeia oa
?i.,1992]. Ia oeae /an iienaii i’youe eean?a iooaoe?e, ui i?ecaiaeyoue
aei ii?ooaiiy ooieoe?? oei?eaeiiai eaiaeo. Ee?i?/iee iie?ii?o?ci IA
iia’ycaiee c oeeie ??ciiiai?oieie iooaoe?yie a aai? O?AI [L.Tsui,1995,
L.C.Tsui, P.Durie,1997]. Aea/aiiy iieaeoey?ii-aaiaoe/ieo iniia IA ni?ey?
?icoi?iith eiai iaoiaaiaco ? iie?ioaiith no?aoaa?? e?eoaaiiy [C.Koch et
al,1993]. Ia no/aniiio aoai? aaaeeeaa cia/aiiy ia? aea/aiiy ca’yceo
aaiioeio c oaiioeiiaeie iniaeeainoyie i?iyao caoai?thaaiiy a iiioeyoe??
Oe?a?ie.

?ica’ycaiiy oeeo ieoaiue a Oe?a?i? aeicaieyoue oaeineiiaeeoe ?aiith
ae?aaiinoeeo IA ? cia/ii iie?ioeoe nai?/ania aaeaeaaoia e?eoaaiiy,
aeoeaia aeeniaina?ia niinoa?aaeaiiy oai?eo ae?oae, a oaeiae aaiaoe/ia
eiinoeueooaaiiy c ianooiiei i?iaaaeaiiyi aeiiieiaiai? ae?aaiinoeee a
?ioi?iaoeaieo ?iaeeiao.

Ca’ycie ?iaioe c iaoeiaeie i?ia?aiaie, ieaiaie, oaiaie

Aeena?oaoe?th aoei aeeiiaii a ?aieao aea?aeaaii? iaoeiai-oaoi?/ii?
i?ia?aie «Caoeno aaiioiiaeo ianaeaiiy Oe?a?ie». Oaia: AeEIO 01.01.01.
/017-92 ? 01. 93. E 020926.

Iaoa ?iaioe

Ioe?ieoe oaiioeiia? i?iyae ci?i a?iioieaaaiaai? nenoaie ? nenoaie
o?aaeaiiy o ae?oae, ui no?aaeaeathoue ia IA, caeaaeii a?ae aaiioeio — c
iaoith iie?ioaiiy i?a- ? iinoiaoaeueii? ae?aaiinoeee oeueiai
caoai?thaaiiy; iioei?coaaoe noaio aaiaoe/iiai eiinoeueooaaiiy ia iniia?
aea/aiiy /anoio iaea?eueo iioe?aieo iooaoe?e aaia O?AI a Oe?a?i?.

Aeey aeinyaiaiiy iinoaaeaii? iaoe aoei noi?ioeueiaaii ianooii?
caaaeaiiy:

1. Aea/eoe ee?i?/i? i?iyae ii?ooaiue a?iioieaaaiaai? nenoaie ? nenoaie
o?aaeaiiy o ae?oae, ye? no?aaeaeathoue ia ioeia?noeeaeic, caeaaeii a?ae
aaiioeio.

2. Aecia/eoe iieacieee o?ce/iiai ?icaeoeo ae?oae, oai?eo ia
ioeia?noeeaeic, caeaaeii iae a?eo, oyaeeino? caoai?thaaiiy ? /ano
anoaiiaeaiiy ae?aaiico.

3. ?ic?iaeoe ?aeiiaiaeaoe?? uiaei oaeineiiaeaiiy aaiaoe/iiai
eiinoeueooaaiiy ? aeiiieiaiai? ae?aaiinoeee a n?i’yo aenieiai ?eceeo
ia?iaeaeaiiy aeeoeie c ioeia?noeeaeicii.

Iaoeiaa iiaecia io?eiaieo ?acoeueoao?a

Aia?oa ia iniia? iiaeeaeaiiai eiiieaeniiai aeine?aeaeaiiy c?iaeaii
ii??aiyeueio oa?aeoa?enoeeo oaiioeiiaeo i?iya?a ci?i a?iioieaaaiaai?
nenoaie ? nenoaie o?aaeaiiy o ae?oae, oai?eo ia IA, caeaaeii a?ae
aaiioeio. O a?oi? aiiiceaio ca iooaoe??th delF508/delF508 a?aecia/aii
iayai?noue oaeeo oneeaaeiaiue, ye iiaaiioi?aen ? ao?ac?y oiiei? eeoee.
Iiaeaii ioe?ieo o?ce/iiai ?icaeoeo ae?oae caeaaeii a?ae aaiioeio, a?eo,
iani-c?inoiaeo ia?aiao??a, oyaeeino? ? o?eaaeino? ia?aa?ao
ioeia?noeeaeico. Iieacaii, ui o ae?oae, oai?eo ia IA, nooi?iue
aeeoaeueii? iaaeinoaoiino? aa??th?oueny iacaeaaeii a?ae iaie?aaoe/iiai
noaoono.

I?aeoe/ia oe?ii?noue io?eiaieo ?acoeueoao?a

Iioeieciaaii noaio aaiaoe/iiai eiinoeueooaaiiy ? aeiiieiaiai?
ae?aaiinoeee ia iniia? aea/aiiy /anoio iaeiioe?ai?oeo iooaoe?e aaia O?AI
a Oe?a?i?. Iieacaii iaiao?aei?noue iieaeoey?ii-aaiaoe/ieo
aeine?aeaeaiue, ni?yiiaaieo ia eeoa ia oai?o aeeoeio, a e ia ??
aaouee?a, oa cae?enithaaieo ?c canoinoaaiiyi i?yii? aeaoaeoe?? iooaoe?e
aaia O?AI ? n?iaeiiai IAe?O- aiae?co.

Aeiaaaeaii aeioe?euei?noue aeei?enoaiiy ?acoeueoao?a
iieaeoey?ii-aaiaoe/ieo aeine?aeaeaiue, i?iaaaeaieo o iiai?e n?i’? i?ae
/an aaiaoe/iiai eiinoeueooaaiiy, ui aeicaiey? cia/ii i?aeaeueoe
ae?aaiinoe/io ?ioi?iaoeai?noue n?iae a?oie aenieiai ?eceeo IA (aei
95,5%). Oea ia? aaaeeeaa iaaeeei-nioe?aeueia cia/aiiy.

O iinoiaoaeuei?e ae?aaiinoeoe? cai?iiiiiaaii canoiniaoaaoe iieacieee
iani-c?inoiaiai ?iaeaeno aeey ioe?iee nooiaiy oyaeeino? ? i?iaiico
ia?aa?ao caoai?thaaiiy, a oaeiae aeey ioe?iee aoaeoeaiino? e?eoaaiiy.

?acoeueoaoe i?iaaaeaiiai aeine?aeaeaiiy cai?iaaaeaeaii a i?aeoeeo ?iaioe
iaaeeei-aaiaoe/ii? eiinoeueoaoe?? ?inoeoooo iaae?ao???, aeooa?noaa ?
a?iaeieia?? AII Oe?a?ie, a?aeae?eaiiy iaaeeoeeie ieiaea. Iaoa??aee
aeena?oaoe?? aeei?enoaii o iaoiaee/ieo ?aeiiaiaeaoe?yo «Ae?aaiinoeea,
e?eoaaiiy oa i?io?eaeoeea ioeia?noeeaeico», Iaeana, 1999. Aeioe?eueiei ?
?oi? iiaeaeueoa ai?iaaaeaeaiiy a e?eoaaeueii-ae?aaiinoe/io ae?yeuei?noue
niaoe?ae?ciaaieo a?aeae?eaiue ? aaiaoe/ieo oeaio??a, ui iaaeathoue
aeiiiiiao oai?ei ia ioeia?noeeaeic.

Iniaenoa o/anoue aeena?oaioa

Aeena?oaoe?eia ?iaioa ? iniaenoei o?oaeii aaoi?a. Naiino?eii cae?eniaii
aeia?? ?ai?acaioaoeaii? a?oie ae?oae, oai?eo ia ioeia?noeeaeic ??ciiai
nooiaiy oyaeeino?. Ocaaaeueiaii ? i?iaiae?ciaaii ?acoeueoaoe ee?i?/iiai
? iieaeoey?ii-aaiaoe/iiai aeine?aeaeaiiy ia?aii? a?oie ae?oae.
I?iaaaeaii aio?iiiiao?e/ia ianoaaeaiiy niinoa?aaeoaaieo ae?oae, iiaeaii
eiai ioe?ieo a ia?oeaioeeyo ? ca iani-c?inoiaei ?iaeaenii. I?iaaaeaii
iaaeeei-aaiaoe/ia eiinoeueooaaiiy ?iaeei aenieiai ?eceeo IA. Naiino?eii
ii?aoeueiaaii ?acoeueoaoe ?iaioe, cae?eniaii noaoenoe/iee aiae?c
io?eiaieo aeaieo ? i?aeaioiaeaii oaeno aeena?oaoe??. ?ic?iaea, aiae?c ?
?ioa?i?aoaoe?y iaoa??aeo, aeeeaaeaiiai a aeena?oaoe??, iaeaaeeoue
aaoi?o.

Ai?iaaoe?y ?acoeueoao?a aeena?oaoe??

?acoeueoaoe i?iaaaeaii? ?iaioe aoei ii?eethaeiaii o aeiiia?ae? ia II
c’?cae? iaaee/ieo aaiaoee?a (i. Aeia-Aoa, 1991), VI c’?cae?
Oe?a?inueeiai oiaa?enoaa aaiaoee?a ? naeaeoe?iia??a ?i. I.?. Aaaeeiaa
(Iieoaaa, 1992), O c’?cae? aeooa??a-a?iaeieia?a Oe?a?ie (Iaeana, 1996),
4-io Iaoe?iiaeueiiio eiia?an? c ioeia?noeeaeico (Iineaa, 1998), II
c’?cae ooec?ao??a ? ioeueiiiieia?a Oe?a?ie (Ee?a,1998)

Ioae?eaoe??

Ii oai? aeena?oaoe?? iioae?eiaaii 11 ?ia?o. O oiio /ene? 4 aeo?iaeuei?
noaoo? (AEo?iae i?aeoe/aneiai a?a/a, 1997; Iaae?ao??y, aeooa?noai oa
a?iaeieia?y, 1998, 1999; ECCACF Newsletter, 1996).

Ianya oa no?oeoo?a ?iaioe

Aeena?oaoe?eia ?iaioa, aeeeaaeaia ia 150 noi??ieao iaoeiiieno,
neeaaea?oueny ?c anooio, iaeyaeo e?oa?aoo?e, 4 ?icae?e?a aeanieo
aeine?aeaeaiue, aiae?co e ocaaaeueiaiiy aeanieo aeine?aeaeaiue,
aeniiae?a, nieneo aeei?enoaieo aeaea?ae. Oaeno aeena?oaoe?? ?ethno?iaaii
25 oaaeeoeyie oa ?enoieaie. Nienie aeei?enoaieo aeaea?ae i?noeoue 183
iacae.

INIIAIEE CI?NO

Ia’?eo oa iaoiaee aeine?aeaeaiiy

Aeey ?ica`ycaiiy iinoaaeaieo caaaeaiue iaie aoei ianoaaeaii 111 ae?oae,
oai?eo ia ioeia?noeeaeic, a?eii iae 3 i?nyoe?a aei 15 ?ie?a ?c 100
?iaeei.

?iciiae?e ca noaooth ? a?eii: oeii/ee?a — 62, ui noaiiaeei 56%, a
ae?a/aoie — 49 — 44% a?aeiia?aeii. Ae?oae aei 1 ?ieo — 57 (51,4%), o
a?oe? 1-3 ?iee — (18%), 4-7 ?ie?a — 23 (20,7%), 8-12 ?ie?a — 9 (8,1%),
i?ney 14 ?ie?a — 2 (11,8%). Ca aoi?/iei neeaaeii niinoa?aaeoaaieo ?iaeei
iaoe??ioe ?iciiae?eyeeny o oaeee niin?a: 86 (77.4%) — oe?a?ioe?, 5
(4,5%) — ?in?yie, 2 (1,8%) — iieaeaaaie, a 18 ae?oae — a?ae ci?oaieo
oetha?a i?ae oe?a?ioeyie ? ?in?yiaie.

On?o oai?eo aoei i?aeaeaii eiiieaeniiio ee?i?/iiio, eaai?aoi?iiio ?
ooieoe?iiaeueiiio ianoaaeaiith, ui aeeth/aei ieceo niaoe?aeueieo
iaoiae?a — AeIE-aiae?c, aiae?c oei?eae?a iioiai? ??aeeie,
?aioaaiieia?/ia ianoaaeaiiy i?aai?a a?oaeii? ee?oeie;
aeaeo?iea?ae?ia?ao?th, aoiea?ae?ia?ao?th, ni??ia?aoeth, OCAe-
ae?aaiinoeeo i?aai?a /a?aaii? ii?iaeieie, aeine?aeaeaiiy ia?oeeaeueii?
iai?oae eenith a e?ia?. Ioe?ieo nooiaiy oyaeeino? caoai?thaaiiy
i?iaiaeeee ca oeaeith Oaaoiaia-A?anoeeaea, ca?aeii c iiaeeo?eaoe??th
A.?a/einueeiai ? I.Eai?aiiaa [1985].

Iieaeoey?ii-aaiaoe/i? aeine?aeaeaiiy, yeeie aoei ioiieaii oai?eo ae?oae,
?oi?o aaouee?a ? nean?a, cae?enieea a?oia iieaeoey?ii? ae?aaiinoeee
niaaeeiaeo oai?ia ?inoeoooo Iieaeoey?ii? a?ieia?? ? aaiaoeee AI Oe?a?ie
(ea??aiee a?oie eaiaeeaeao a?ieia?/ieo iaoe E.A. E?aoeoeue). AeIE-aiae?c
aeeth/aa aecia/aiiy naie iooaoe?e o 7, 10, 11 aeciiao aaia O?AI:
delF508, 1677 delTA (10 aecii), R553X, G551D (11 aecii),
R334W,1154insTC, del5491 (7 aecii), a oaeiae n?iaeiee aiae?c iie?ii?oieo
AeIE — ia?ea??a, u?eueii c/aieaieo ?c aaiii IA o nenoaiao (KM-19/Pstl
XV2C TGg1 ? J3. 11Pst). ?aeaioeo?eaoe?y iooaoe?e cae?enithaaeany ca
aeiiiiiaith iie?ia?acii? eaioethaiai? ?aaeoe?? neioaco AeIE (IOe?)
[J.Kenneth et al,1990], ?c ianooiiith ?aeaioeo?eaoe??th iayaiino? aai
a?aenooiino? a?aeiia?aeieo iooaoe?e ca aeiiiiiaith aeaeo?ioi?aco.
Niaoeeo?/i?noue IOe? aecia/aeany ia?ith ie?aii?aeia??a, eiiieaiaioa?ieo
e?ioeyi oeaieoth/eo ae?eyiie aiie?o?eaoe??. IOe? i?iaiaeeee ia
oa?iioeeeea?? «Perkin Elmer» (o??ia «Cetus», NOA) ca noaiith,
cai?iiiiiaaiith Salki [R.K. Saiki et al,1988]. Ca ?acoeueoaoaie
AeIE-aiae?co a 57,2% aeiaaee?a aeyaeaii oae? iooaoe?? aaia O?AI: delF508
— 56,3%; R553X — 0,45%; G551D — 0,45%, ? oai?eo ae?oae aoei iiae?eaii ia
o?e aaiioeiia? a?oie: ia?oa — ?c aaiioeiii delF508/delF508, ae?oaa —
delF508/x ? o?aoy — x/x.

Ae?aaiic i?aeoaa?aeaeoaaany i?aeaeuaiith eiioeaio?aoe??th oei?eae?a
iioo, ui noaiiaeea a na?aaeiueiio ii a?oi? 96,38+3,87 iiieue/e.
Aecia/aiiy eiioeaio?aoe?? aeaeo?ie?o?a o iio? aeeiioaaeiny ca
aeiiiiiaith i?eiea?i?iiaiai aeaeo?ioi?aco ca iaoiaeii A?aniia ? Eoea,
[L.Gibson, R.E Cooke,1959]. I?aeaeuaiiy eiioeaio?aoe?? oei?eae?a iioiai?
??aeeie a?aecia/aeiny o an?o aaiioeiiaeo a?oiao (oaaeeoey 1).

A?e, o yeiio aia?oa ae?aaiinooaaany ioeia?noeeaeic, eieeaaany a?ae 1
i?nyoey aei 14 ?ie?a ? ii a?oi? a na?aaeiueiio noaiiaea 19,15+3,18
i?nyoey.

Oaaeeoey 1

Na?aaei? aaee/eie eiioeaio?aoe?? aeaeo?ie?o?a iioo (iiieue/e) o ae?oae,
oai?eo ia ioeia?noeeaeic, caeaaeii a?ae oyaeeino? caoai?thaaiiy ?
aaiioeio

A?oie ca

aaiioe-

iii Caaeia?eueiee

ia?aa?a Na?aaeiuei-

oyaeeee

ia?aa?a Oyaeeee

ia?aa?a Na?aaei?

cia/aiiy

aeaeo?ie?oo 1. delF508/

delF508

n = 44

101,0 + 1,0

106,9 + 6,6

101,6 + 4,9

103,0 + 3,92. delF508/x

n = 36 83,9 + 12,8 84,8 + 6,0 93,9 + 4,9 89,0 + 3,83. x-/-x

n = 30 76,5 + 8,1 93,3 + 5,2 99,2 + 7,1 94,8 + 4,4

A?eueo?noue niinoa?aaeoaaieo ae?oae iio?aieee aei ee?i?ee a ia??iae
caaino?aiiy a?iioieaaaiaaiai i?ioeano (?o ianoaaeoaaee o?eueee
oi?iaeiaae oeueiai ia??iaeo).

Ca aeaieie ee?i?ei-aaiaaeiae/iiai aiaiiaco, on? oai?? ae?oe aoee
ia?iaeaeai? a?ae caei?iaeo aaouee?a. Na?aaei?e a?e aaouee?a aei iiiaioo
iieia?a: iaoe — 24,7 ?ie?a, aaoueei — 26.5 ?ie?a.

O aeine?aeaeoaaieo oai?eo ae?oae ia?o? iciaee caoai?thaaiiy aeyaeyeeny:
a?ae ia?iaeaeaiiy — o 53 ae?oae (47,7%); o a?oe? aei 3-o i?nyoe?a — o 33
(29,7%), aei iaeiiai ?ieo — o 20 (18%). Oaeei /eiii, o a?eueoino? ae?oae
(106 oai?eo, 95%) ia?o? ee?i?/i? iciaee caoai?thaaiiy ?icaeaaeeny aaea
ia ia?oiio ?ioe? aeeooy.

A?aeiia?aeii aei aeaieo ee?i?/ii? ea?oeie e ia’?eoeaiiai aeine?aeaeaiiy,
ci?oaia oi?ia ioeia?noeeaeica niinoa??aaeany o 88 ae?oae (79,3%); o 8
aeiaaeeao (7,2%) — eaaaiaaa oi?ia, o 15 aeiaaeeao (13,5% %) — eeoeiaa
oi?ia (oaaeeoey 2).

Oaaeeoey 2

?iciiae?e oai?eo ia ioeia?noeeaeic ca oi?iith caoai?thaaiiy

caeaaeii a?ae aaiioeio

O i ? i a del508/delF508 del F508/ x x / xO n ue i a i
caoai?thaaiiye?euee. %e?euee. %e?euee %e?euee. Ci?oaia 38 86,4 30 81,1
20 66,6 8879,3 Eaaaiaaa— 3 8,1 5 16,7 8 7,2 Eeoeiaa 6 13,6 4 10,8 5
16,7 1513,5 Onueiai 44 39,6 37 33,4 30 27,0 111

Ci?ie o noai? a?iioieaaaiaai? nenoaie ia ia?oiio ?ioe? aeeooy iinoaee o
88% ae?oae. Na?aaei?e a?e i?iyao ?ani??aoi?iiai neiae?iio noaiiaea 5,3
i?nyoey. O 22 ?c oeeo ae?oae (23,4%) ?ani??aoi?iee neiae?ii iinoaa aei
ia?oiai i?nyoey aeeooy. Ia?oeie eiai i?iyaaie aoei eaaea iieaoeeoaaiiy
(aac aai ia oii? ?ani??aoi?ii? a??onii? ?ioaeoe??) ?c iinooiiaei
?icai?oaiiyi oa?aeoa?ieo ee?i?/ieo i?iya?a oai?iae: caoyaeiee aai
iino?eiee i?enooiiiiae?aiee eaoaeue c aeaaeith, ai?eiith aaaeei
a?aeoa?eoaaiith iie?ioith, aieia? o?eie a eaaaiyo, ui caa??aathoueny
i?ney e?ea?aeaoe?? aino?eo yaeu.

Na?aaei?e a?e i?iyao eeoeiaiai neiae?iio noaiiaea 2,1+0,3 i?nyoey. O 38
aeiaaeeao (37%) eeoeiaee neiae?ii ?icii/aany a?ae ia?iaeaeaiiy. O 16
ae?oae (14,4%) caoai?thaaiiy iai?oanooaaei iaeii??aei ?eaonii.

C-iii?ae oneeaaeiaiue caoai?thaaiiy aeeaaiinoiaaii: niiioaiiee
iiaaiioi?aen (3,6%), aoaeaeoac (5,4%), na?oeaai-eaaaiaaa iaaeinoaoi?noue
?c ?icaeoeii eaaaiaaiai na?oey (26,1%) ? eiai aeaeiiiainaoe??th (4,4%),
a?e?a?iee oee?ic ia/?iee (2,7%). O ia??iae? niinoa?aaeaiiy o 6,7%
a?aecia/aeeny iciaee aino?iai neioneoa, 3,3% ae?oae iaee iieeiic
iiniaeo oiae?a, 5,6% — aaeaii?aee II ? III nooiaiy.

Aeey eiiieaenii? ioe?iee o?ce/iiai ?icaeoeo aeei?enoiaoaaee ye
ia?oeaio?euei? noaiaea?oe, oae ? iani-c?inoiaee ?iaeaen (IC?),
?ic?iaeai? I.M. Tanner, ui aeicaieya ioe?ieoe iieacieee iane o?ea o
ca’yceo c ?inoii (ii?iith aaaaea?oueny IC? a?ae 110 aei 90 a?aenioe?a)
[Iaco??i A.A. ? ?i.,1985; I.M. Tanner et al, 1966].

Iani-c?inoiaee ?iaeaen ?ic?aoiao?oueny o oaeee niin?a:

(oaeoe/ia aaaa)/(?aeaaeueia aaaa a?aeiia?aeii aei c?inoo ? noao?) o
100%.

A?aenoaaaiiy o o?ce/iiio ?icaeoeo aoei aeyaeaii o 87 (78,4%) ae?oae
noiniaii aaae e o 72 (64,8%) noiniaii c?inoo (iani-c?inoia? iieacieee
ieae/? ca 10 ia?oeaioee?a). I?e oeueiio ae?aci? ii?ooaiiy (iaio ye 3
ia?oeaioeey) noiniaii aaae aeyaeaii o 58,6% oai?eo, noiniaii c?inoo — o
37,7%. Na?aaei? iieacieee aaae o an??? a?oi? noaiiaeee 12,72+1,85
ia?oeaioee?a, c?inoo — 25,0+3,1 ia?oeaioee?a. Iani-c?inoiaee ?iaeaen aoa
ieae/ee ca ii?io ? aei??aithaaa 84,3% o an??? a?oie.

?aioaaiieia?/ia ea?oeia caeaaeaea a?ae o?eaaeino? oai?iae, oyaeeino?
noaio ? oace caoai?thaaiiy. Iaea?eueo oa?aeoa?iith aoea caaaeueia
aio?caiaoici?noue (68%), a oaeiae ii?aeiaiiy ae??aiiaoeueicieo caeooo?a
?c noiauaiiyi no?iie a?iio?a, e?eueoeaiiae?aieo ? e?i?eieo ooai?aiue,
e?no (60%) ia oii? aeainoi?iiiueiai aeeooc?eiiai eaaaiaaiai ?enoiea.
?aioaaiieia?/iee ?iaeaen o na?aaeiueiio ii a?oi? aei??aithaaa 12,20+0,64
aaeai.

Aeine?aeaeaiiy ooieoe?? ciai?oiueiai iiaeeoo o a?eueoino? oai?eo ae?oae
(14 oai?eo — 85%) aeyaeei eiia?iiaaio oi?io aaioeeyoe?eieo ii?ooaiue, a
o aeaio ae?oae — ?ano?oeoeaio oi?io. O 28% ae?oae iieacieee ooieoe??
ciai?oiueiai iiaeeoo aoee a ii?i?. Aaioeeyoe?eio iaaeinoaoi?noue I-II
nooiaiy aoei aeyaeaii o o?ueio oai?eo, III nooiaiy — o 4-o ae?oae, IV
nooiaiy — o 3-o ae?oae. Aiae?c aeaieo aeaeo?iea?ae?ia?aie aeyaea o
a?eueoino? oai?eo (86%) ii?ooaiiy iaoaaie?/ieo i?ioean?a o i?iea?ae?
a?iiene/iiai oa?aeoa?o; aoei oaeiae neioniao oao?ea?ae?th (72,4%),
ia?aaaioaaeaiiy i?aaeo a?aeae?e?a na?oey (30,6%). Aoiea?ae?ia?ao?y
aeyaeea o 10 (10,2%) oai?eo a?ia?o?io?th i?iea?aea i?aaiai oeoii/ea, o
42%) oai?eo — cieaeaiiy nei?ioiino? i?iea?aea.

Aeey aiae?co aeaieo canoiniaaii iaoiae ia?aeiiiai noaoenoe/iiai
oii?yaeeoaaiiy, aeenia?n?eiee, ei?aeyoe?eiee, aeene?ei?iaioiee ?
?aa?an?eiee iaoiaee. Aeey iiaiiai aeyaeaiiy aieeao aaiioeio ia i?iyae
ee?i?/ieo iciae caoai?thaaiiy ie aaeaeeny aei ?ioaa?aeueieo iieaciee?a.
Aeey ?oiuei? ioe?iee canoiniaoaaeany aaoi?nueea iaoiaeeea I.TH.
Aioaiiiiaa [I.Aioaiiiia, 1991]. Oii?yaeeoaaiiy cae?enithaaeiny ia
ia?niiaeueiiio eiii’thoa?? a iaeao? «Statistica» [I.Ieioea? oa ?i.,1991;
A.Iaeneiia oa ?i.,1983; A.Eae?i,1980; I.Aioaiiiia, 1991].

?acoeueoaoe aeine?aeaeaiiy oa ?o iaaiai?aiiy

A?iioieaaaiaa? ci?ie aeii?iothoue o ee?i?/i?e ea?oei? ioeia?noeeaeico,
aecia/athoue eiai ia?aa?a ? i?iaiic. C iaoith aea/aiiy ca’yceo i?ae
oeiii iooaoe?? ? ee?i?/ieie aa??aioaie i?io?eaiiy ?ani??aoi?iiai
i?ioeano iaie aoei aea/aii iniaeeaino? o?aaeaiiy a?iioieaaaiaai? nenoaie
o ae?oae caeaaeii a?ae aaiioeio. O a?oi? aiiiceaio a?aecia/a?oueny ?aiiy
iai?oanoaoe?y caoai?thaaiiy, o 62% ae?oae ia?o? iciaee caoai?thaaiiy
iinoaee a?ae ia?iaeaeaiiy, o o?aoeie ?c ieo aoee i?iyae oeiiaiai
?ani??aoi?iiai neiae?iio (nooee eaoaeue a?aioe?, i?enooiiiiae?aiee,
iiaeaeiee eieethoiiiae?aiee, ?c aaaeei a?aeie?aiethaaiith aeaaeith
iie?ioith). O 38% aeiaaee?a iciaee caoai?thaaiiy c’yaeeeny o 6-i?ny/iiio
a?oe?. Ia ia?oiio ?ioe? aeeooy o 94% ae?oae ?icaeioany ?ani??aoi?iee
neiae?ii. Na?aaei?e a?e eiai i?iyao noaiiaeoue o a?oi? 3,2+0,76 i?nyoey.
Na?aaeiy aaee/eia PaO2 — ia?aiao?a, yeee iaeae?aci?oa a?aeaeca?eaeth?
eeniao?ainii?oio ooieoe?th i?aai?cio, aei??aithaaea 61,1+2,81 ii ?o. no.
O oe?e a?oi? caaino?aiiy a?iioieaaaiaaiai i?ioeano aoee iae/ano?o? e
i?io?eaee iaeaaae/a (ia c?acie iiaaiii?? o 84%). Aeey ?aioaaiieia?/ii?
ea?oeie aoee oa?aeoa?i? caeoooy eaaaiaai? oeaieie (a?ia??ioeyoe?y),
iineeaiiy ? aeaoi?iaoe?y a?iioinoaeeiiiai ?enoiea, ina?aaeeia?, ??aeoa
naaiaioa?i? ? /anoeia? ?io?eueo?aoe. ?aioaaiieia?/iee ?iaeaen ca
A?anoeeaeii aei??aithaaa o oe?e a?oi? 10,5 aaea. O 16% ae?oae
a?iioieaaaiaaee i?ioean a?aeaoaaany ?c aoyaoaaiiyi a?iio?a ??ciiai
eae?a?o, ia c?acie a?iio?oo.

Oaaeeoey 3

Nooi?iue aeeoaeueii? iaaeinoaoiino? ae?oae, oai?eo ia ioeia?noeeaeic,

caeaaeii a?ae aaiioeio

Nooi?iue aeeoaeueii? iaaeinoaoiino? Aiiiceaioe ca delF508/delF508
Aaoa?iceaioe ca delF508/ x x / x

AeI 0 no. —26,34,2AeI I no. 12,925,016,7 AeI II no. 25,834,029,1 AeI
III no. 58,031,350,0 AeI IV no. 3,33,0—

sse aeaeii c oaaeeoe? 3, c?noaaeaiiy ee?i?/ieo ? ooieoe?iiaeueieo
iieaciee?a o a?oi? delF508/delF508 aeyaeei o 2/3 ae?oae AeI-III no.
(Z=2,69, p<0,007), ui na?ae/eoue i?i a?eueo aaaeeee, ii??aiyii c ae?oueie II a?oie, ia?aa?a o?ii?/iiai a?iioieaaaiaaiai i?ioeano II a?oie. Ae?oe iin?? ia?aeaioeo?eiaaieo iooaoe?e iin?aeaee i?ii?aeia i?noea — i?ae oai?eie I ? II a?oie, ui i?aeoaa?aeaeo?oueny noaoenoe/ii (p<0,01). O aeine?aeaeoaaieo a?oiao oai?eo aaaeeee ia?aa?a caoai?thaaiiy a?aecia/aany a 77,3% (I a?oia), 48,7% (II a?oia), 60% (III a?oia) aeiaaee?a a?aeiia?aeii (p<0,05). I?ia?anoaaiiy o?ii?/iiai a?iioieaaaiaaiai i?ioeano a oe?e a?oi? i?ecaiaeeei aei ?yaeo oneeaaeiaiue. Oaea a??cia oneeaaeiaiiy ye iiaaiioi?aen o iaoiio aeine?aeaeaii? a?aecia/aeiny a 10% aeiaaee?a ? o?eueee o ae?oae oe??? a?oie. Ca?aeii c e?eoa??yie, iaaaaeaieie o e?oa?aoo??, eaaaiaai-na?oeaaee neiae?ii (cor pulmonale) aoei ae?aaiinoiaaii o 38% ae?oae oe??? a?oie [I.?.Eai?aiia ? ?i., 1995]. I?iaaaeaiee aiae?c aeaieo aiaiiaco, aaeueii? ioe?iee ? ia?aee?i?/i? aeine?aeaeaiiy iieacaee ae?aciee ee?i?/iee iie?ii?o?ci ci?i o a?iioieaaaiaa?e nenoai? o ae?oae ?? a?oie. ?aiiy iai?oanoaoe?y caoai?thaaiiy a?ae ia?iaeaeaiiy niinoa??aaeany aeaui ??aeoa (o 35%), o ia?o? o?noue i?nyoe?a - o 89%, a aei e?ioey ia?oiai ?ieo aeeooy — o 100% ae?oae. Caoai?thaaiiy c iaeiaeiaith /anoioith ?icii/eiaeiny ye ?c ?ani??aoi?iiai, oae ? c eeoeiaiai neiae?iio. O 82% ae?oae ?ani??aoi?iee neiae?ii ?icaeioany ia ia?oiio ?ioe? aeeooy. Na?aaei?e a?e eiai i?iyao noaiiaea 3,9+1,3 i?nyoey. Caaino?aiiy a?iioieaaaiaaiai i?ioeano c aoyaoaaiiyi ia?aio?ie eaaai?a ia c?acie iiaaiii?? i?io?eaee eaaoa ? cono??/aeeny o 63% ae?oae, a ia c?acie a?iio?oo — o 37%. Aaee/eia PaO2 cieaeoaaeany aei 65,4+1.9 ii ?o. no. Aeeoaeueio iaaeinoaoi?noue III nooiaiy aoei aeyaeaii o?eueee o o?aoeie oai?eo ae?oae, oiae? ye o 26% ae?oae oaeeo ci?i aeyaeaii ia aoei. I?ia?anoaaiiy o?ii?/iiai a?iioieaaaiaaiai i?ioeano i?ecaaei aei oi?ioaaiiy "cor pulmonale" o 33% ae?oae oe??? a?oie. ?iaeaen Oaaoiaia, ieae/ee ca 40 aae?a, a?aecia/aii o 49% ae?oae. Na?aae iin??a ia?aeaioeo?eiaaieo iooaoe?e i?iyae caoai?thaaiiy a?ae iiiaioo ia?iaeaeaiiy a?aecia/aeeny o 30% oai?eo ae?oae, o 85% aeiaaee?a eiai iciaee c`yaeeeny aei e?ioey ia?oiai ?ieo aeeooy, a o 15% — i?ney iaeiiai-aeaio ?ie?a aeeooy. Caoai?thaaiiy ii/eiaeiny c ?ani??aoi?iiai neiae?iio o 53% oai?eo. Na?aaei?e a?e ii/aoeo i?iyao ?ani??aoi?iiai neiae?iio noaiiaeoue 8,6+1,3 i?nyoey. Caaino?aiiy ia c?acie iiaaiii?? a?aecia/ai? o 68%, ia c?acie a?iio?oo — o 32%. Paioaaiieia?/iee ?iaeaen ca A?ano?eaeii aei??aith? 9,1 aaea, PaO2 – 63,2+2.8 ii ?o. no. AeI-I?? nooiaiy aecia/aii o 50% ae?oae. "Nor pulmonale" - o 20%. ?iaeaen Oaaoiaia, ieae/ee ca 40 aae?a, aoa o 60% ae?oae. I?iaaaeai? ee?i?/i? aeine?aeaeaiiy ? ?yae iieaciee?a, ui oa?aeoa?ecothoue nooi?iue o?aaeaiiy a?iioieaaaiaai? nenoaie, - oei caaino?aiiy (iiaaiii?y), iecuee? iieacieee ?aI2, a?eueo ?aiiy iiyaa iciae caoai?thaaiiy, ioe?iea ca oeaeith Oaaoiaia, — na?ae/eee i?i a?eueo aaaeeee ee?i?/iee ia?aa?a a?iioieaaaiaaiai i?ioeano a ia?o?e a?oi? (p<0,05). O ae?oa?e a?oi? a?aecia/aany ae?aciee ee?i?/iee iie?ii?o?ci ci?i a?iioieaaaiaai? nenoaie. O o?ao?e a?oi? aeine?aeaeoaai? iieacieee iin?aeaee i?ii?aeia i?noea i?ae ia?oith ? ae?oaith a?oiaie. Aeey ioe?iee aieeao aaiioeio ia ee?i?/iee i?iya o?ii?/iiai a?iioieaaaiaaiai i?ioeano iaie aoei ?ic?iaeaii ?ioaa?aeueiee iieaciee, yeee niieo/aa oyaee?noue ia?aa?ao caoai?thaaiiy a aaeao ca Oaaoiaiii, oei eiai caaino?aiiy, AeI, oyaee?noue ia?aa?ao, ioe?ieo ?aioaaiieia?/iiai ?iaeaeno ca A?anoeeaeii. Na?aaei? cia/aiiy ?ioaa?aeueiiai iieacieea noaiiaeei a I, II, oa III a?aeiia?aeii - 0,72+0,03; 0,56+0,05; 0,61+0,05; p<0,05). Ii??aiyiiy cae?enithaaeiny ca ?aiaiaei eiao?oe??ioii Nie?iaia, aaee/eia yeiai — ns=0,19 (p<0,05), ui na?ae/eoue i?i iayai?noue anioe?aoe?? i?ae aaiioeiii ? ee?i?/ieie i?iyaaie o?ii?/iiai a?iioieaaaiaaiai i?ioeano. Iao? niinoa?aaeaiiy ? aeai? aaoi??a [L.C.Tsui,1995; L.C.Tsui., P.Durie, 1997; ICFC,1996] i?i ca'ycie i?ae oeiii iooaoe?? ? oaiioeiiaeie i?iyaaie ci?i o a?iioieaaaiaa?e nenoai? a?aeaeaathoue ?oith aa??aaaeuei?noue a aaiioeiiaeo a?oiao, ui aeaco? ia a?aenooi?noue aei?noeiai aaiaoe/iiai eiio?ieth aaia IA ia nooi?iue oyaeeino? i?iyaeaiiy ii?ooaiue ooieoe?? a?iioieaaaiaai? nenoaie. Aeey ioe?ithaaiiy ca'yceo aieeao aaiioeio ia ii?ooaiiy nenoaie o?aaeaiiy aoei aea/aii iniaeeaino? oa?aeoa?o ? nooi?iue o?aaeaiiy i?aai?a oeoieiai-eeoeiaiai o?aeoo o an?o aaiioeiiaeo a?oiao. O a?oi? aiiiceaio o eiaeii? ae?oai? aeeoeie ia?oei i?iyaii caoai?thaaiiy aoa eeoeiaee neiae?ii, na?aaei?e a?e i?iyao yeiai ii a?oiao noaiiaea a?aeiia?aeii 1,4+0,3 i?nyoey, 2,2+0,49 i?nyoey ? 3,1+1,1 i?nyoey (p1-2<0,05; p1-3<0,05). Ana oea na?ae/eoue i?i aeoaea ?aii? aoyaoaaiiy i?aeoeoieiai? caeice a iaoieia?/iee i?ioean o a?oi? aiiiceaio. Ee?i?/i? i?iyae eeoeiaiai neiae?iio aoee iaea?eueo ae?aci? o ae?oae ? a?oie, oa?aeoa?iith iciaeith eiai aoee /ano?, aei 8-10 ?ac?a ia aeiao, aeii?iaeiaiiy (iiaeaeiee — aei 30) (p1-2<0,006; p1-3<0.01). Aeeniaioe/i? aeii?iaeiaiiy (??aee? aai eaoiiiae?ai?) a??ia?aeii iae/ano?oa cono??/aeeny a oe?e a?oi? (p1-3<0,001). Aiie oaeiae iae/ano?oa a?aecia/aeeny aaeeeith e?euee?noth, aoee aee?i? oa nia?aeth/? (p1-3<0,05). Ca?eueoaiiy aeeaioa aiane?aeie iaoai?ecio ? a?iioii?? i'yc?a a?aecia/aeiny a oe?e a?oi? o 65% ae?oae. I?aeoaa?aeaeaiiyi ca'yceo i?ae nooiaiai iaie?aaoe/ii? iaaeinoaoiino? (II) ? oyaee?noth eeoeiaiai neiae?iio ? iayai?noue iiceoeaii? ei?aeyoe?? i?ae aeae?eaiiyi iaeo?aeueiiai aee?o ? /anoioith aeii?iaeiaiiy (R=0,62, p<0,01). I?ae /an eii?ieia?/iiai aeine?aeaeoaaiiy iayai?noue iaeo?aeueiiai aee?o a?aecia/aeany a on?o ianoaaeaieo ae?oae ia?oi? a?oie (Z=2,35, p1-3<0,016), iayai?noth aee?ieo eeneio o 72,9% (p1-3<0.05), i'yciaeo aieieii (e?aaoi?ay) o 54% (p<0,05). Ne?ae cacia/eoe, ui oeueo?acaoeiaa aeine?aeaeaiiy i?aeoeoieiai? caeice oai?eo ae?oae cia/ieo ?ica?aeiinoae noiniaii ci?ie ?? ianyao ? no?oeoo?e ia aeyaeei. O 87% oai?eo ae?oae aiiiceaio ca delF508 niinoa??aaeeny ??ciiiai?oi? aa??aioe o?aaeaiiy i?aaio - a?ae iacia/iiai ca?eueoaiiy ?ici???a caeice, ae?eyiie i?aeaeuaii? aoiaaiiino? aei ae?aaeaiiai ou?eueiaiiy on??? caeice, i?e/iio a ?aii?o noaae?yo caoai?thaaiiy. Iaeia?oa ? iaeaaae/a iciaea aeenooieoe?? caeic oiieiai eeoa/ieea - iaeii?aeueiue ?eaon - a?aecia/aeany o 22,7% oai?eo ae?oae oe??? a?oie (p<0,05), oea ca?aa?oueny c aeaieie ca?oa?aeieo aaoi??a [A.Hamosh et al, 1991]. O 5 oai?eo aoei ae?aaiinoiaaii ao?ac?th oiiei? eeoee. O a?oi? ae?oae aaoa?iceaio ca iooaoe??th delF508 ia?oee i?iya caoai?thaaiiy ia neiae?ii ii?ooaiiai o?aaeaiiy a?aecia/aany o eiaeii? 5-? aeeoeie. Nooi?iue ae?aciino? eeoeiaeo i?iya?a aoa oaeiae aeinoaoiuei ae?aciee o ae?oae oe??? a?oie, aea iaio, ai?ae o ia?o?e a?oi?. I?ae /an eii?ieia?/iiai aeine?aeaeaiiy iayai?noue iaeo?aeueiiai aee?o aoei a?aecia/aii o 92% oai?eo ae?oae. ??ci? aa??aioe o?aaeaiiy i?aeoeoieiai? caeice cono??/aeeny o 65% oai?eo, iaeii?aeueiee ?eaon - o 8% aeiaaee?a. Na?aae ae?oae-iin??a ia?aeaioeo?eiaaieo iooaoe?e caoai?thaaiiy ii/eiaeiny c eeoeiaiai neiae?iio o 30% aeiaaee?a. Ee?i?/i? i?iyae eeoeiaiai neiae?iio a oe?e a?oi? aoee iaeiaio ae?aci?. Ioi?ieai? aeii?iaeiaiiy o 30% ae?oae iae/ano?oa cono??/aeeny a oe?e a?oi?. Ca?eueoaiiy aeeaioa aoei a?aecia/aii o 40%. O a?oi? oai?eo ae?oae c ia?aeaioeo?eiaaieie iooaoe?yie i?ae /an eii?ieia?/iiai aeine?aeaeaiiy ci?ie aoee iaio ae?aci?. Aaee/eie oaeeo iieaciee?a ye iaeo?aeueiee aee?, aee?i? eeneioe ? e?aaoi?ay a?aecia/aeeny a?aeiia?aeii a 84,5%, 53,8% ? 30,8% aeiaaee?a. O 55% oai?eo ae?oae a?aecia/aeeny ??ci? aa??aioe o?aaeaiiy i?aeoeoieiai? caeice. Iaeii?aeueiee ?eaon cono??/aany o 3 ae?oae (10%), a o iaeiiai c ieo aaiioei aoa G551D/x. I?aeoaa?aeaeaiiyi aieeao aaiioeio ia aecie?eiio ooieoe?th i?aeoeoieiai? caeice ? iayai?noue iaie?aaoe/ii? iaaeinoaoiino? (II) o ae?oae, oai?eo ia ioeia?noeeaeic, ui aeyaey?oueny ye ii?ooaiiy anei?eyoe?? aee?o. Ee?i?/ii oea — iaaeinoaoi? ca?eueoaiiy aaae, ae?aciee eeoeiaee neiae?iiii, a?eueo ?aii?e ii/aoie caoai?thaaiiy ? iaioa o?eaae?noue aeeooy. Oaaeeoey 4 I?iya iaie?aaoe/ii? iaaeinoaoiino? caeaaeii a?ae aaiioeio Aaiioei II IAe e?euee?noue %e?euee?noue delF508/ delF508 n=44 44 100,0 delF508/ x n=37 34 91,9 3 8,1 x/ x n=30 25 83,3 5 16,7 A?aeiia?aeii aei aiae?co ee?i?/ieo iciae (oaaeeoey 4) o oai?eo ae?oae aiiiceaio ca delF508 (100%) a?aecia/a?oueny iaea?eueo ae?acia II, ui oa?aeoa?eco?oueny noaaoi?a?th, ae?a?a?th, iaoai?eciii, ? o 70% aiia i?iyaeeany a?ae ia?iaeaeaiiy, ui i?aeoaa?aeaeaii o ?iaioao ?ioeo aeine?aeiee?a [L.C.Tsui et al,1997]. O a?oi? ae?oae aaoa?iceaio ca iooaoe??thdelF508 ae?acia iaie?aaoe/ia iaaeinoaoi?noue a?aecia/aeany o 91,9%, o a?oi? IA ae?oae ?c ia?aeaioeo?eiaaieie iooaoe?yie - o 73,3% (p<0.05). Aeey ioe?iee aea/aiiy iniaeeainoae ee?i?/ieo i?iya?a ? ?acoeueoao?a eaai?aoi?ii-?ino?oiaioaeueiiai ianoaaeaiiy i?aai?a oeoieiai-eeoeiaiai o?aeoo ca iayaiino? IA iaie aoee aecia/aii ?ioaa?aeuei? ia?ai?ii? aeey eiaeii? aaiioeiiai? a?oie (I - 0,73+0,02; II - 0,49+0,04; III - 0,47+0,05), eiao?oe??io ia?ii? ei?aeyoe?? noaiiaea R=0,47, p<0,001, ui na?ae/eoue i?i o?niee ca'ycie i?ae aaiioeiii - “aaaee?” iooaoe?? (cie?aia, aiiiceaioe ca delF508) ? nooiaiai iaie?aaoe/ii? iaaeinoaoiino?. I?e c?noaaeaii? aeaieo oeueo?acaoeiaiai ? iaeueiaoi?iiai iaoiae?a aeine?aeaeaiiy iaie aoei aeyaeaii aaiaoiiaaae?th a aaiioeiiaeo a?oiao ianoaaeaieo ae?oae — o 79,2%, 46,2% ? 60,0% aeiaaeeao a?aeiia?aeii. O a?oi? aiiiceaio aaiaoiiaaae?y cono??/aeany /ano?oa (?2 = 7,16; p1-2<0,05). Oeueo?acaoeia? iciaee oieanoaco (ou?eueiaiiy no?iie noaeei ? aeia/ieo i?ioie, iineeaiiy aoiaaiiino? ia?aio?ie) aoee aeu? a a?oi? aiiiceaio ca delF508 (/2=31,6; p1-2<0,05, p1-3<0,05); aeia/iieai'yio oai?iao ia aeyaeaii o aeiaeiiai oai?iai. Ca aeaieie aooiin??, aeeiiaii? o 33 ae?oae a?eii a?ae 0 aei 5 ?ie?a, aee?iao aeeno?io?th aoei ae?aaiinoiaaii o ae?oae a on?o a?oiao o 41%, 40%, 33% aeiaaee?a a?aeiia?aeii. Aiaeii/an o o?ueio ae?oae I a?oie iaei i?noea ii?aeiaiiy aeeooc?eii? aee?iai? aeeno?io?? c i?iyaaie oieanoaco, ui ca?aa?oueny c aeaieie e?oa?aoo?e [E.I.Nieieiaa,1990]. I?ae /an iaoiai aeine?aeaeaiiy ia aoei aeyaeaii i?aeaeuaiiy aeoeaiino? ?iaeeeaoi?ieo oa?iaio?a, ui oa?aeoa?ecothoue no?oeoo?io oe?e?ni?noue aaiaoioeeo?a, a oaeiae ee?i?/ieo iciae ? a?aeiia?aeieo eaai?aoi?ieo iieaciee?a ia/?ieiai? iaaeinoaoiino?, ui a?aeiia?aea? a?aeiiiio iiaeyaeo noiniaii ia/anoeo ?? i?iya?a ca iayaiino? ioeia?noeeaeico [A.A.Iaaeia oa ?i., 1992; E.A.Aiaaeaiiaa,1988; G.Santis et al,1991]. Ii??aiyeueiee aiae?c ?acoeueoao?a aea/aiiy ooieoe?iiaeueiiai noaio ia/?iee aeyaea ?? ci?ie a 13,9% 22,6% ? 16,7% aeiaaee?a a?aeiia?aeii. Aiae?c i?ioa?iia?aie ia aeyaea aeeaieeo ii?ooaiue a?eeiai?-neioaoe/ii? ooieoe?? ia/?iee, i?ioa iii??i? yaeua aeeni?ioa?iai?? a?aecia/aeeny a a?oi? aiiiceaio o 83% oai?eo ae?oae, ?ica?aeiino? noaoenoe/ii aeinoia??i? (p<0,05). Ioe?iea ?acoeueoao?a eaai?aoi?ieo iaoiae?a aeine?aeaeaiiy iieacaea ?oith iaaeinoaoith ?ioi?iaoeai?noue, oiae? ye oeueo?acaoeiaee iaoiae aeine?aeaeaiiy ? aoaeoeaiei aeey i?eaeeoo?ai? ae?aaiinoeee iaoieia?/ieo ci?i o ia/?ioe?. Iao? aeai? na?ae/aoue, ui oyaee?noue o?aaeaiiy aaiaoia?e?a?ii? nenoaie aecia/a?oueny iayai?noth a aaiioei? oai?i? aeeoeie aeaio “aaaeeeo” iooaoe?e aiiiceaioe ca delF508 (R=0,59; p<0,001). Oea i?ecaiaeeoue aei ooai?aiiy a?eueo aeaaei? aeia/?, ui ni?ey? iiya? iano?oeoe?? aeia/ieo i?ioie ? aeia/iiai iooe?y. A on?o aeine?aeaeoaaieo a?oiao iaie aoei i?iaaaeaii ei?aeyoe?eiee aiae?c nooiaiy aeeoaeueii? iaaeinoaoiino? ? e?eueeino? iaeo?aeueiiai aee?o. Ei?aeyoe?eiiai ca'yceo oeeo iieaciee?a ia anoaiiaeaii. Oea na?ae/eoue i?i oa, ui a?iioieaaaiaa? ii?ooaiiy aa??ththoueny iacaeaaeii a?ae iaie?aaoe/iiai noaoono. Inoaoi/ia oaiioeiiaa aeni?aneai?noue aecia/a?oueny ia o?eueee O?AI -aaiioeiii, a e iiaea iiaeoethaaoeny ye ?ioeie aaiaoe/ieie /eiieeaie, oae ? aaaioaie iaaeieeoiueiai na?aaeiaeua. Ne?ae i?eionoeoe, ui aaiioei aecia/a? ??aaiue oaiioeiiai? i?ieeaino?, a ia oi?ioaaiiy inoaoi/iiai oaiioeio aieeaathoue ?io? /eiieee. Ona aeuaiaaaaeaia na?ae/eoue i?i oa, ui ca'ycie i?ae aaiioeiii ? oaiioeiii ia ? aaniethoiei ? ioaea oyaeaiiy i?i iueiai ia iiaeooue aooe ni?iuaieie. Aeine?aeaeaiiy a oeueiio iai?yieo iathoue ? iaaeae? o?eaaoe, ui ni?eyoeia cai?iaaaeaeaiith iiaeo iaoiae?a a?eueo ?aoe?iiaeueii? oa?ai?? i?e oeueiio caoai?thaaii?. Iieacieee, ui oa?aeoa?ecothoue nooi?iue o?aaeaiiy a?iioieaaaiaai? nenoaie ? nenoaie o?aaeaiiy, ? ee?i?/i? niinoa?aaeaiiy na?ae/aoue, ui caoai?thaaiiy a a?oi? iin??a ia?aeaioeo?eiaaieo iooaoe?e i?io?ea? aeinoaoiuei aaaeei. Aeoiaey/e c oeueiai, iiaeia i?eionoeoe iayai?noue a Oe?a?i? ua iaei??? iaaei?ii? “aaaeei?” iooaoe??. Iiooee a oeueiio iai?yieo iathoue o?eaaoe. Cia/iee aeao?oeeo aaae o?ea (iaio ye 3 ia?oeaio?ey) anoaiiaeaii a?aeiia?aeii ca a?oiaie o 81%, 72,3% oa 50% ae?oae (p<0,05). A?aenoaaaiiy uiaei ?inoo (iaio ye 3 ia?oeaio?ey) a?aei?/aeiny o 64,8%, 55,9% oa 42,3% ianoaaeaieo a?aeiia?aeii. Aiae?c iieaciee?a o?ce/iiai ?icaeoeo ca Tanner oaeiae aeyaea cieaeaiee iieaciee iane o?ea o an?o ianoaaeaieo ae?oae aei 73,5+2.1; 79,2+1.8, 77+0.35 a?aenioe?a oa IC? aei 80,5+1.9; 85,8+2.0; 83,6+2.6 a?aenioe?a. O ae?oae ia?oi? a?oie iaei i?noea cieaeaiiy ye eiaeano iane, oae ? IC? (p<0.05). Ei?aeoe?y ioo?eoeaiiai noaio iio?aao? a?eueo aia?a?eieo caoiae?a aeey ae?oae oe??? a?oie. Iaie i?iaiae?ciaaii caeaaei?noue IC? a?ae oyaeeino? oa o?eaaeino? ia?aa?ao caoai?thaaiiy. O a?oi? aiiiceaio IC? ciaioo?oueny i?iii?oe?iiaeueii o?eaaeino? ia?aa?ao caoai?thaaiiy a?ae 97% o ae?oae a?eii iaioa 1 ?ieo aei 65% o ae?oae 14 e?oiueiai a?eo (p<0,05) O ae?oa?e a?oi? oeae iieaciee cieceany c 85% o ae?oae a?eii iaioa iaeiiai ?ieo aei 80% o ae?oae i?ney 4 ?ie?a (p<0,05). O o?ao?e a?oi? a?aei?/aeiny ??aiii??ia cieaeaiiy iieaciee?a IC? a on?o a?eiaeo a?oiao aac a??ia?aeii? ??cieoe?. A on?o aaiioeiiaeo a?oiao aeyaeaii cieaeaiiy iieaciee?a A?? caeaaeii a?ae oyaeeino? caoai?thaaiiy. I?e oyaeeiio ia?aa?ao (?iaeaen Oaaoiaia a?eueoa 40) o oai?eo ae?oae ia?oi? a?oie a?aei?/aii cieaeaiiy iieacieea iane aei 70,7+2.2 oa IC? aei 78,8+13,4 (p<0,05). Oaeei /eiii, o a?oi? aiiiceaio ca delF508 a?aenoaaaiiy ae?oae o o?ce/iiio ?icaeoeo a??ia?aeii a?eueo ae?aaeaia, ai?ae a ?ioeo aeine?aeaeaieo a?oiao. A?aoiaoth/e cacia/aia, aeioe?eueiei ? canoinoaaiiy iieaciee?a o?ce/iiai ?icaeoeo ae?oae aeey aecia/aiiy nooi?iy oyaeeino?, i?iaiico ia?aa?ao caoai?thaaiiy oa ioe?iee aoaeoeaiino? e?eoaaiiy. Cai?iaaaeaeaiiy aeinyaiaiue iieaeoey?ii? aaiaoeee a i?aeoeeo aaiaoe/iiai eiinoeueooaaiiy ? aeiiieiaiai? ae?aaiinoeee a?aee?eei iiao a?o o i?io?eaeoeoe? oeueiai aaaeeiai niaaeeiaiai caoai?thaaiiy a ?iaeeiao aenieiai ?eceeo ia?iaeaeaiiy aeeoeie c ioeia?noeeaeicii, oiio ui c'yaeeany iiaeeea?noue ae?aaiinooaaoe caoai?thaaiiy ia iniia? ?aeaioeo?eaoe?? ia?aeiiiai aaiaoe/iiai aeaoaeoo. Aoei i?iaaaeaii aaiaoe/ia eiinoeueooaaiiy a 96 ?iaeeiao aenieiai ?eceeo ia?iaeaeaiiy ae?oae ?c IA ?c ??cieo ?aa?ii?a Oe?a?ie c aeei?enoaiiyi ?acoeueoao?a iieaeoey?ii-aaiaoe/ieo aeine?aeaeaiue. ?acoeueoaoe aeine?aeaeaiue aeicaieeee ?icae?eeoe oe? ?iaeeie ia ae?aaiinoe/ii ?ioi?iaoeai? (a yeeo iiaeeeaa ?aeaioeo?eaoe?y IA o?iiinii a iaio aaouee?a), iai?a?ioi?iaoeai? (?aeaioeo?eo?oueny iaeia IA o?iiiniia) ? ia?ioi?iaoeai?. Iniiaiee aianie a ?ioi?iaoeai?noue ianoaaeaieo iaie ?iaeei aiineoue iooaoe?y delF508, ui o?aieyeany c /anoioith 56%; iooaoe?? R553X ? G551D — a iiiaeeiieeo aeiaaeeao. Ca ?acoeueoaoaie AeIE-aiae?co oanoiaai? iooaoe?? aoei aeyaeaii ia iaio o?iiiniiao o 40 ?iaeeiao; o 20 ?iaeeiao - o?eueee ia iaei?e o?iiinii?, a ?ioa aoea ia?e??iaaia IAe?O-ia?ea?ii, a 7 ?iaeeiao aoei i?ae?a?aii ?ioi?iaoeai? ia?ea?e aeey iaio o?iiinii. Oaeei /eiii, 67% ?iaeei aoee ae?aaiinoe/ii ?ioi?iaoeai?, ui aeicaiey? i?iaiaeeoe a ieo iieaeoey?ii-aaiaoe/i? aeine?aeaeaiiy a iiaiiio ianyc?, 14% ?iaeei aoee iai?a?ioi?iaoeai?, iiaeeeaith ? ?aeaioeo?eaoe?y o?eueee iaei??? IA o?iiiniie aai i?yiei oanooaaiiyi iooaoe?e, aai aiae?cii c/aieaiiy ia?ea??a AeIE. O oeeo ?iaeeiao iiaeeeaei ? cae?eniaiiy AeIE-aiae?co aeey ooi/iaiiy aaiaoe/iiai ?eceeo oa i?iaaaeaiiy aeiiieiaiai? ae?aaiinoeee. ? o?eueee 15 ?iaeei (15,5%) aeyaeeeny ae?aaiinoe/ii ia?ioi?iaoeaieie. Aeiiieiaiao ae?aaiinoeeo a oeeo ?iaeeiao iiaeia cae?enieoe o?eueee aecia/eaoe oa?iaioe iaaeieiie?aeii? ??aeeie. Iiaieo ?iaeei aenieiai ?eceeo IA (iaeaeaa aaoueee ? aeeoeia) aoei ianoaaeaii 74, ?c ieo o 71 aoei ?aeaioeo?eiaaii iaeaea? IA - o?iiiniie i?yiith aeaoaeoe??th aaia ? n?iaeiei IAe?O-aiae?cii, o 2 ?iaeeiao o?eueee iaeio o?iiiniio aoea ia?e??iaaii iie?ii?oieie eieonaie, a iaei?e ?iaeei? ?o i?ae?a?aoe ia aaeaeiny. Ioaea, ae?aaiinoe/ia ?ioi?iaoeai?noue a aeaiiio ?ac? noaiiaeoue 95,6%, ui aeicaiey? a noi i?ioeaioao aa?aiooaaoe ia?iaeaeaiiy caei?iai? aeeoeie. Aeey i?iniaeoeaiiai aaiaoe/iiai eiinoeueooaaiiy iaiao?aeiei ? i?iaaaeaiiy, o.ca. "eaneaaeiiai", iieaeoey?ii-aaiaoe/iiai ne?ei?iao iooaoe?e na?aae aeecueeeo ?iaee/?a i?iaaiaea, o yeiai aaeaeiny ?aeaioeo?eoaaoe iooaoe??, a oaeiae o aaouee?a oai?i? aeeoeie ? ?oi?o ia?oia??a i?e iiaoi?ieo oethaao. A?aenooi?noue oanoiaaieo iooaoe?e, a ?ioiai ia?oia?a aeicaiey? iiaeeo?eoaaoe ?ecee aaoa?iceaioiiai iin?enoaa a?ae caaaeueiiiiioeyoe?eiiai 1:24 aei 1:50, ? ?ecee iaoe oai?o aeeoeio noa? 1/50 o 1/4 = 1/200 (0,5%) ca /anoioe iooaoe?? delF508 56%. A aeaiee /an aiae?c iooaoe?e aeicaiey? aeiiiiiaoe aeecueeei ?iaee/ai oai?iai ia IA. O ?iaee/?a oai?eo I ? II nooiaiy e?aaiino?, o eio?eo delF508 cono??/a?oueny ia iaio o?iiiniiao, oiaoi aiiiceaio ca oe??th iooaoe??th, a ?ac? a?aenooiino? oanoiaaii? iooaoe?? iiaeeea?noue iaoe oai?o aeeoeio c IA i?aeoe/ii aeeeth/aia. A ?ac? iayaiino? o oai?iai ia IA oanoiaaieo iooaoe?e ia iaei?e o?iiinii?, aeioe?eueii aeine?aeaeoaaoe ?iaee/?a I ? II nooiaiy e?aaiino? (neae?ia?a, aeyaeuee?a, o?oie, eocai?a ? ?i.). Io?eiai? ?acoeueoaoe iiaeia aeei?enoiaoaaoe aeey ?ic?aooie?a aaiaoe/iiai ?eceeo. Ia no/aniiio aoai? noaio i?iaeaie IA a Oe?a?i? aoaeoeaiei iaoiaeii ai?ioueae c iei ? aeiiieiaiaa ae?aaiinoeea, yea ia? ia iao? ooi/iaiiy iayaiino? o ieiaea oeueiai aaaeeiai niaaeeiaiai caoai?thaaiiy. Aeey i?aiaoaeueii? ae?aaiinoeee oeueiai caoai?thaaiiy canoiniao?oueny i?yia aeaoaeoe?y aaia, a oaeiae n?iaeiee aiae?c c/aieaieo iie?ii?oieo AeIE - ia?ea??a ?c eieonii aaia O?AI. O aeayeeo aeiaaeeao ia oaea?oueny i?ae?a?aoe aeey ?iaeeie ?ioi?iaoeaio iie?ii?oio AeIE-nenoaio, iae/ano?oa /a?ac oa, ui iaia aeeaiai i?iaaiaea, ? i?aiaoaeueia ae?aaiinoeea i?iaiaeeoueny aecia/aiiyi oa?iaio?a i?e?iai?neiie eeoa/ieea ieiaeo a aii?ioe/i?e ??aeei?. O 32 ?iaeeiao aoei i?iaaaeaii 43 aeiiieiaia? ae?aaiinoeee, oiio ui a 9 ?iaeeiao aoee iiaoi?i? aaa?oiino? (o 2 ?iaeeiao ii o?e aaa?oiino?). Iaea?aeaiiy iaoa??aeo aeey aeiiieiaiai? ae?aaiinoeee i?iaiaeeeiny ca aeiiiiiaith ?iaaceaieo aeine?aeaeaiue, oaeeo ye a?iin?y oi??iio aai ieaoeaioe e aii?ioeaioac. 43-i aaa?oiei ae?iie aoei i?aeaeaii 45 ?iaaceaiei aeine?aeaeaiiyi (o aeaio - ii aeaa aeine?aeaeaiiy - a?iin?y oi??iio e aii?ioeaioac). O ia?oiio o?eiano?? aoei i?iaaaeaii 22 (48,9%) a?iin?? oi??iio, o ae?oaiio o?eiano?? - 12 (26,7%) aeiin?e ieaoeaioe ? 11 aii?ioeaioac?a (24,4%). O ia?oiio o?eiano?? ?iaaceai? aeine?aeaeaiiy aoee aeeiiai? a ?iaeeiao, aea aaiaoe/ia eiinoeueooaaiiy ? ieaioaaiiy aeiiieiaiai? ae?aaiinoeee i?iaiaeeeiny aei aaa?oiino?. A 19 ?iaeeiao (44,2%) aoei i?iaaaeaii i?yiee aiae?c iooaoe?e delF508, a 5 ?iaeeiao (11,6%) i?iaiaeeeiny eiia?ioaaiiy i?yiiai aiae?co c aecia/aiiyi ia?ea??a c/aieaieo ?c eieonii O?AI. 11 ?iaeei (25,6%) iio?aaoaaee eiia?ioaaiiy i?yiiai aiae?co c aecia/aiiyi oa?iaio?a a aii?ioe/i?e ??aeei?, aea oea aoei aeeiiaii o?eueee o 2 ?iaeeiao, oiio ui 5 aaa?oieo ae?iie ae??oeee ia?a?aaoe aaa?oi?noue ?c ?eceeii 50/50; a ?ioeo aeiaaeeao i?e i?iaaaeaii? i?yiiai aiae?co a?iioaoa oi??iio ieiaee aoee caei?ia?. A 8 ?iaeeiao (18,6%) aeiiieiaiaa ae?aaiinoeea i?iaiaeeeany o?eueee aeine?aeaeaiiyi oa?iaio?a aii?ioe/ii? ??aeeie. [?inoeooo aeooa?noaa ? a?iaeieia?? ?i. Iooa, i. Naieo-Iaoa?ao?a, eaai?aoi??y i?aiaoaeueii? ae?aaiinoeee niaaeeiaeo oai?ia - ea??aiee i?io. A.N. Aa?aiia]. I?ney AeIE-aiae?co io?eiaiiai iaoa??aeo a 15-oe aeiaaeeao o ieiae?a aoei ae?aaiinoiaaii ioeia?noeeaeic, o 5 aeiaaeeao — ?c eiia??i?noth 50%, o 27 aeiaaeeao ieiaee aoee caei?ia?, na?aae ieo 16 aaoa?iceaioieo iin??a aaia. A on?o aeiaaeeao ae?aaiinoiaaiiai ioeia?noeeaeico, ca aeiyoeii iaei??? ?iaeeie, on? aaa?oiino? aoei ia?a?aaii. O 5 iai?a?ioi?iaoeaieo ?iaeeiao, aea ?ecee aoa 50:50, aoei ae??oaii ia?a?aaoe aaa?oi?noue?. Iaea?eueo aoaeoeaiei ? eiinoeueooaaiiy ?iaeeie ? ieaioaaiiy aeiiieiaiai? ae?aaiinoeee aei ianoaiiy aaa?oiino?, ui ni?ey? nai?/aniiio ? iaeneiaeueiiio aeei?enoaiith on?o iayaieo iaoiae?a aeiiieiaiai? ae?aaiinoeee. Ne?ae cacia/eoe, ui nai?/ania aaiaoe/ia eiinoeueooaaiiy ? aeiiieiaiaa ae?aaiinoeea ia iniia? ?acoeueoao?a AeIE-aiae?co iiceoeaii aieeaathoue ia ?ai?iaeoeoeaio iiaaae?ieo ?iaeeie. Ii?aeiaiiy coneeue niaoe?ae?no?a iaae?ao?e/ieo ee?i?e, e?ea??a-aaiaoee?a, iieaeoey?ieo a?ieia?a, oao?aoe?a aeiiieiaiai? ae?aaiinoeee a iao?e ?iaio? ni?eyei eiiieaeniiio ae??oaiith i?iaeai, ui noiyoue ia?aae ?iaeeiaie c ae?oueie, oai?eie ia ioeia?noeeaeic: a) i?aeaeuaiiy ??aiy ?icoi?iiy aaoueeaie oai?i? aeeoeie niaaeeiai? i?e?iaee aeaiiai caoai?thaaiiy; a) i?iaaaeaiiy AeIE-aiae?co i?iaaiaeo, eiai aaoueeai, a?aoai, nano?ai oiui aeey noai?aiiy aaieo aeaieo iin??a aaia IA; a) iaaeaiiy aeiiiiiae o iiaeaeueoiio ieaioaaii? ?iaeeie, a oaeiae nai?/ania e aoaeoeaia canoinoaaiiy aeiiieiaiai? ae?aaiinoeee c iaoith i?io?eaeoeee oeueiai aaaeeiai niaaeeiaiai caoai?thaaiiy. Aeniiaee 1. A?oia aiiiceaio ca iooaoe??th delF508 oa?aeoa?eco?oueny a?eueo aaaeeeie ee?i?ei-ooieoe?iiaeueieie ?ani??aoi?ieie ii?ooaiiyie, aeieeiaiiyi eaaaiaaeo oneeaaeiaiue (iiaaiioi?aen o 10%, aoaeaeoac -18%), ui aecia/a?oueny iayai?noth anioe?aoe?? (RA=0,19, p<0,05) i?ae aaiioeiii ? ee?i?/ieie i?iyaaie o?ii?/iiai a?iioieaaaiaaiai i?ioeano. 2. A?aecia/aii o?niee ca'ycie i?ae aaiioeiii “aaaee?” iooaoe??, cie?aia aiiiceaio ca delta F508 ? nooiaiai iaie?aaoe/ii? iaaeinoaoiino? o ae?oae, oai?eo ia ioeia?noeeaeic (R=0,47, p<0,001)). Aiaeia?/ia caeaaei?noue niinoa??aa?oueny a oe?e a?oi? oai?eo ae?oae noiniaii oaiioeiiaieo iciae o?aaeaiiy aaiaoia?e?a?ii? nenoaie (R=0,59; p<0,001). 3. A on?o aaiioeiiaieo a?oiao a?aecia/a?oueny ca?eueoaiiy eiioeaio?aoe?? oei?eae?a iioiai? ??aeeie, ui na?ae/eoue i?i ?noioio ?ieue aaia ioeia?noeeaeico o aecia/aii? oaiioeio iioiaeo caeic. 4. Aio?iiiiao?e/i? iieacieee iiaiia?iaeaeaieo ?c ioeia?noeeaeicii oae? nai? ye o i?aeoe/ii caei?iaeo ae?oae. Iaaeae? a?aeaoaa?oueny a?aenoaaaiiy ?o o o?ce/iiio ?icaeoeo, yea iaea?eueo ae?acia o a?oi? aiiiceaio ca delF508. Cieaeaiiy iani-c?inoiaeo iieaciee?a caeaaeeoue a?ae o?eaaeino?, oyaeeino? caoai?thaaiiy, oa?i?io anoaiiaeaiiy ae?aaiico ? ii/aoeo canoinoaaiiy iaoiaaiaoe/ii? oa?ai??. 5. I?e aaiaoe/iiio eiinoeueooaaii? ?iaeei aenieiai ?eceeo ioeia?noeeaeica, c iaeyaeo ia iaaenieo /anoioo iaea?eueo iioe?aieo iooaoe?e aaia O?AI, iaia'yceiaei ? aeei?enoaiiy ?acoeueoao?a i?yiiai ? iai?yiiai AeIE-aiae?co, i?iaaaeaiiai oai??e aeeoei? ? eiai aaoueeai, ui i?aeaeuo? ae?aaiinoe/io ?ioi?iaoeai?noue ?iaeei aei 95,5%. 6. Aoaeoeaiith i?io?eaeoeeith ioeia?noeeaeico a ae?aaiinoe/ii ?ioi?iaoeaieo ?iaeeiao ? einieaenia canoinoaaiiy i?yii? aeaoaeoe?? aaia ? n?iaeiiai aiae?co IAe?O ia?ea??a aeey ?aeaioeo?eaoe?? iooaioieo o?iiinii i?e aeiiieiaia?e ae?aaiinoeoe? caoai?thaaiiy, ui aa?aioo? ia?iaeaeaiiy caei?iai? aeeoeie. Nienie iioae?eiaaieo iaoeiaeo i?aoeue, ye? a?aeia?aaeathoue iniiai? iieiaeaiiy aeena?oaoe??. 1. Ieoaeeaoe E.I. Ioeiaenoeeaeic: aaiaoe/aneia eiinoeueoe?iaaiea e aei?iaeiaay aeeaaiinoeea // AEo?iae i?aeoe/aneiai a?a/a ? 2,1997, n.27 -29. 2. Ieoaeeaoeue E.I., Aioeie?i TH.A. Anioe?aoe?y aaiioeio c iniaeeainoyie ee?i?/ieo i?iya?a ci?i a?iioieaaaiaai? nenoaie i?e ioeia?noeeaeic? o ae?oae // Iaae?ao??y, aeooa?noai oa a?iaeieia?y N5, 1998 n.26-29. 3. Livshits L.A., Kravchenko S.A., Mikhaylets L.P., Sopko N.I. Mutation screening results // ECCACF Newsletter, 1996, v.3,N 2, p. 3-4. 4. E.I.Ieoaeeaoeue Aieea o?eaaeino?, oyaeeino? ia?aa?ao ioeia?noeeaeico oa oeio iooaoe?? ia o?ce/iee noai oai?eo ae?oae. // Iaae?ao??y, aeooa?noai oa a?iaeieia?y N4, 1999 n.151 5. Iiioeyoeeiiiue e naiaeiue aiaeec annioeeaoeee IAe?O-ia?ea?ia n aaiii ioeiaenoeeaeica a iaeioi?uo ?aaeiiao Oe?aeiu //Eeaoeoe E.A., A?eoei A.I., E?aa/aiei N.A., O?aiia A.A., Ieoaeeaoe E.I., Au/eiaa A.I., Ai?iaaiei I.A., Aaa?eethe TH.I., Eaauaiei O.Y., Aa?aiia A.N., Aoaeeaaneay O.I.//Aoi?ie ananithciue nuacae iaaeeoeeineeo aaiaoeeia, Aeia-Aoa,1990, 4-6 aeaeaa?y (Oacenu aeieeaaeia), Iineaa, 1990, 253-254. 6. AeIE-aiaeec iooaoeee a aaia o?ainiaia?aiiiai aaeea ioeiaenoeeaeica (O?AI) e oa?aeoa? eo annioeeaoeee n iieeii?oeciii aeeeiu ?ano?eeoeeiiiuo o?aaiaioia iaeioi?uo eieonia o?iiiniiu 7 a ?aciuo ?aaeiiao Oe?aeiu // E.A. Eeaoeoe, N.A. E?aa/aiei, A.E. A?eoei, E.I. Ieoaeeaoe, I.A. Ai?iaaiei, A.I.Au/eiaa, O.E. Aoaeeaaneay, I.E. Eiaaeue/oe, TH.E.Aaa?eethe, A.N.Aa?aiia // Oacenu aeieeaaeia. VI nuacae Oe?aeineiai iauanoaa aaiaoeeia e naeaeoeeiia?ia ei. I.E. Aaaeeiaa (Iieoaaa, 1992 a.), Oii.I, n. 80. 7. E?aa/aiei N.A., A?eoei A.E., Ieoaeeaoe E.I., Niiei I.E., Ai?aeeaiei E.TH., Aa?iiioaaeyi I.I., Eeaoeoe E.A. I?aiaoaeueiay aeeaaiinoeea iaeioi?uo ianeaaenoaaiiuo caaieaaaiee a Oe?aeia, iniiaaiiay ia aiaeeca AeIE. // Oeueo?acaoeiaa ia?eiaoaeueia ae?aaiinoeea, 1994, ? 4-5, n.90-95. 8. Oeueo?acaoeiaia enneaaeiaaiea i?aaiia a?thoiie iieinoe i?e ioeiaenoeeaeica o aeaoae. // Ieoaeeaoe E.I., Aaaei N.A., Aioeieei TH.A. // Aoia?ao?y a ia?eiaoieia??, a?iaeieia?? oa iaae?ao???. III ui??/iee ca??iee iaoeiaeo i?aoeue Oe?a?inueei? anioe?aoe?? e?ea??a oeueo?acaoeiai? ae?aaiinoeee a iaae?ao??? oa a?iaeieia??. E?eaee ??a, 1995, n.267-268. 9. Ieoaeeaoeue E.I., Oa?aio?iaa I.I., E?aoeoeue E.A., E?aa/aiei N.A., Ia?/aiei I.A. Aeiiieiaiaa ae?aaiinoeea a n?i’yo aenieiai ?eceeo ia?iaeaeaiiy ae?oae c ioeia?noeeaeicii // X c’?cae aeooa??a-a?iaeieia?a Oe?a?ie (Oace aeiiia?aeae), Iaeana, 1996,n.91. 10. Analysis of cystic fibrosis in Ukraine /L.A.Livshits, S.Kravchenko, M. Nechiporenko, L.P.Mickhaylets, N.Sopko // DNA Extraction and Cystic Fibrosis Mutation Detection Techniques. Prague, Sept. 13-16, 1997, p.9-10. 11. Iieaeoey?ii-aaiaoe/iee aiae?c ioeia?noeeaeico a Oe?a?i? // E?aoeoeue E.A., E?aa/aiei N.A., Ia/eii?aiei I.A., Ieoaeeaoeue E.I., Aa?aoc E.A., Niiei I.?. // Iaoa??aee iaoeiai-i?aeoe/ii? eiioa?aioe?? "No/aniee noai iaaee/ii? aaiaoeee a Oe?a?i?" Ee?a, 19-20 o?aaiy 1999 ?.,n.99-100. ?oeiien aeena?oaoe?? ia caeiaoooy a/aiiai nooiaiy eaiaeeaeaoa iaaee/ieo iaoe ca niaoe?aeuei?noth 03.00.15 - aaiaoeea. Oe?a?inueeee iaoeiaee a?a??i?/iee oeaio? IIC Oe?a?ie. Ee?a,1999. A aeena?oaoe?? iieacaia ii??aiyeueia oa?aeoa?enoeea ee?i?/ieo i?iya?a ii?ooaiue a?iioieaaaiaai? nenoaie oa nenoaie o?aaeaiiy caeaaeii a?ae aaiioeio o 111 ae?oae oai?eo ia ioeia?noeeaeic (IA) o a?oe? a?ae 1 i?nyoey aei 15 ?ie?a. Ca ?acoeueoaoaie AeIE-aiaeeco a 57,2% aeiaaee??a aeyaeaii oae? iooaoe?? aaia O?AI: delF508 - 56,3%; R553X - 0,45%; G551D - 0,45%. Oai?eo ae?oae aoei iiae?eaii ia o?e aaiioeiia? a?oie: ia?oa - ?c aaiioeiii delF508/delF508 (39,6%), ae?oaa - delF508/x (33,4%) ? o?aoy - x/x (27%). Aeaia ioe?iea o?ce/iiai ?icaeoeo ae?oae caeaaeii a?ae aaiioeio, cai?iiiiiaaii aeei?enoiaoaaoe oe? iieacieee aeey ioe?iee nooiaiy oyaeeino? ? i?iaiico ia?aa?ao caoai?thaaiiy. Iioei?ciaaia noaia aaiaoe/iiai eiinoeueooaaiiy oa aeiiieiaiai? ae?aaiinoeee, ui aeicaieeoue cia/ii i?aeaeueoe ae?aaiinoe/io ?ioi?iaoeai?noue ?iaeei a?oie aenieiai ?eceeo IA (aei 95,5%). Oea ia? aaaeeeaa iaaeeei-nioe?aeueia cia/aiiy. Ia oaio aeena?oaoe?? iioae?eiaaii 11 iaoeiaeo i?aoeue. ?oeiienue aeenna?oaoeee ia nieneaiea o/aiie noaiaie eaiaeeaeaoa iaaeeoeeineeo iaoe ii niaoeeaeueiinoe 03.00.15 - aaiaoeea. Oe?aeineee iao/iue aeaeaie/aneee oeaio? IC Oe?aeiu. Eeaa, 1999. Aaiaoe/aneea iiaeoiaeu a oeo/oaiee caei?iauey ianaeaiey noaiiayony ana aieaa ?ani?ino?aiaiiuie. Iiaua aaiaoe/aneea oaoiieiaee e iaoiaeu aeeaaiinoeee iaoneaaeeaatho iaiaoiaeeiinoue ia?aniio?a e oniaa?oainoaiaaiey nouanoaothueo oi?i i?ioeeaeoeee, ea/aiey e ?aaaeeeoaoeee ianeaaenoaaiiuo caaieaaaiee. E?oiiui aeinoeaeaieai a eco/aiee IA yaeyaony ea?oe?iaaiea aaia o?ainiaia?aiiiai aaeea (O?AI) a 1989 aiaeo, /oi iicaieeei ?ac?aaioaoue iaoiaeu iieaeoey?iie aeeaaiinoeee aeaiiiai caaieaaaiey. Ioe?uoea aaia IA auei nii?yaeaii n aieueoeie iaaeaaeaeaie ia auno?ue i?aeoe/aneee ?acoeueoao, ii ieacaeinue, /oi yoi aaaeiia niauoea yaeyaony anaai eeoue ia/aeii aeieaiai e o?oaeiiai iooe e iaeaa/aieth o/anoe ethaeae, no?aaeathueo yoei caaieaaaieai. Neaaeothuei yoaiii, ia iaiaa cia/eoaeueiui, /ai naii ioe?uoea aaia yaeyaony iniuneaiea i?ioeannia, i?ienoiaeyueo a i?aaiecia iineoaey aaiia, i?eaiaeyueo e caaieaaaieth. A ianoiyuee iiiaio iienaii iyoue eeannia iooaoeee, eioi?ua i?eaiaeyo e ia?ooaieth ooieoeee oei?eaeiiai eaiaea. Eeeie/aneee iieeii?oeci IA naycai n yoeie ?acee/iuie iooaoeeyie a aaia O?AI. Eco/aiea iieaeoey?ii-aaiaoe/aneeo iniia IA niinianoaoao iiieiaieth aai iaoiaaiaca e oeo/oaieth no?aoaaee ea/aiey. Ia nia?aiaiiii yoaia aaaeiia cia/aiea eiaao eco/aiea aeeyiey aaiioeia ia oaiioeie/aneea iniaaiiinoe i?iyaeaiey caaieaaaiey a iiioeyoeee Oe?aeiu. A aeenna?oaoeee ia iniiaa oaeoaeaiiiai eiiieaeniiai enneaaeiaaiey iieacaia n?aaieoaeueiay oa?aeoa?enoeea eeeie/aneeo i?iyaeaiee a?iioieaai/iie e ieuaaa?eoaeueiie nenoai a caaeneiinoe io aaiioeia o 111 aeaoae, no?aaeathueo ioeiaenoeeaeicii (IA) a aic?anoa io 1 ianyoea aei 15 eao. Iieaeoey?ii-aaiaoe/aneea enneaaeiaaiey i?iaiaeeenue aieueiui aeaoyi, eo ?iaeeoaeyi e neanai. AeIE-aiaeec aeeth/ae ii?aaeaeaiea naie iooaoeee a 7, 10, 11 yeciiao aaia O?AI: delF508, 1677 delTA (10 yecii), R553X, G551D (11 yecii), R334W,1154insTC, del5491 (7 yecii), a oaeaea naiaeiue aiaeec iieeii?oiuo AeIE ia?ea?ia, oanii noeaieaiiuo n aaiii IA a nenoaiao (KM-19/Pstl; XV2C / TGg1 e J3.11Pst). Ii ?acoeueoaoai AeIE-aiaeeca a 57,2% neo/ayo auyaeaiu iooaoeee aaia O?AI: delF508 - 56,3%; R553X - 0,45%; G551D - 0,45%. Aieueiua aeaoe auee ?acaeaeaiu ia o?e aaiioeie/aneea a?oiiu: ia?aay - n aaiioeiii delF508/delF508 (39,6%), aoi?ay - delF508/x (33,4%) e o?aouey - x/x (27%). I?iaaaeaiiua eeeie/aneea enneaaeiaaiey e ?yae iieacaoaoaeae, oa?aeoa?ecothuea noaiaiue ii?aaeaiey a?iioieaai/iie nenoaiu, - oei iaino?aiey (iiaaiiiey), ieceea iieacaoaee ?aI2, aieaa ?aiiaa iiyaeaiea i?eciaeia caaieaaaiey, ioeaiea ii oeaea Oaaoiaia, aicieeiiaaiea ineiaeiaiee (iiaaiioi?aen) naeaeaoaeuenoaiaaee i aieaa oyaeaeii eeeie/aneii oa/aiee a?iioieaai/iiai i?ioeanna a ia?aie a?oiia (p<0,05). Ai aoi?ie a?oiia ioia/aeny au?aaeaiiue eeeie/aneee iieeii?oeci eciaiaiee a?iioieaai/iie nenoaiu. A o?aoueae a?oiia enneaaeiaaiiua iieacaoaee caieiaee i?iiaaeooi/iia iieiaeaiea iaaeaeo ia?aie e aoi?ie a?oiiaie. Niaeanii aiaeeco eeeie/aneeo i?eciaeia o aieueiuo aeaoae aiiiceaio ii delF508 (100%) ioia/aaony iaeaieaa au?aaeaiiay iaie?aaoe/aneay iaaeinoaoi/iinoue, oa?aeoa?ecothuayny noaaoi?aae, aeea?aae, iaoai?eciii. A a?oiia aeaoae aaoa?iceaio ii iooaoeee delF508 au?aaeaiiay iaie?aaoe/aneay iaaeinoaoi/iinoue ioia/aeanue o 91,9%, a a?oiia IA aeaoae n iaeaeaioeoeoee?iaaiiuie iooaoeeyie - o 73,3% (p<0.05). A a?oiia aaoa?iceaio ii delF508 eeoa/iue neiae?ii i?ioaeae eaa/a, /ai o aiiiceaio, ii aieaa oyaeaei, /ai a a?oiia aieueiuo n iaeaeaioeoeoee?iaaiiuie iooaoeeyie. Iieacaii, /oi iaeiieaeueiue eeaon a aeaa ?aca /aua ano?a/aeny a a?oiia aiiiceaio ii delF508 - a 22,7% neo/aaa (p<0,01). Aeaia ioeaiea oece/aneiai ?acaeoey aeaoae a caaeneiinoe io aaiioeia, aic?anoa, iani-?inoiauo ia?aiao?ia, oyaeanoe e aeeeoaeueiinoe oa/aiey ioeiaenoeeaeica. I?aaeeiaeaii eniieueciaaoue iieacaoaee iani-?inoiaiai eiaeaena aeey ioeaiee noaiaie oyaeanoe e i?iaiica i?ioaeaiey caaieaaaiey, a oaeaea ioeaiee yooaeoeaiinoe ea/aiey. Iioeiece?iaaia noaia aaiaoe/aneiai eiinoeueoe?iaaiey e aei?iaeiaie aeeaaiinoeee ia iniiaa eco/aiey /anoio iaeaieaa ?ani?ino?aiaiiuo iooaoeee aaia O?AI a Oe?aeia. Iieacaia oeaeaniia?aciinoue eniieueciaaiey ?acoeueoaoia iieaeoey?ii-aaiaoe/aneeo enneaaeiaaiee, i?iaaaeaiiuo a iieiie naiuea i?e aaiaoe/aneii eiinoeueoe?iaaiee, /oi iicaieyao cia/eoaeueii iiauneoue aeeaaiinoe/aneoth eioi?iaoeaiinoue naiae a?oiiu aunieiai ?enea IA (aei 95,5%). Yoi eiaao aaaeiia iaaeeei-nioeeaeueiia cia/aiea. A 32-o naiueyo auea i?iaaaeaia aei?iaeiaay aeeaaiinoeea. Iieo/aiea iaoa?eaea aeey aei?iaeiaie aeeaaiinoeee i?iaiaeeeinue iin?aaenoaii eiaaceaiuo enneaaeiaaiee, oaeeo eae aeiiney oi?eiia eee ieaoeaiou e aiieioeaioac. Iinea AeIE-aiaeeca iieo/aiiiai iaoa?eaea a 15-oe neo/ayo o ieiaeia aue aeeaaiinoe?iaai ioeiaenoeeaeic, a 5-oe neo/ayo n aa?iyoiinoueth a 50%, a 27-o neo/ayo ieiaeu auee caei?iau, n?aaee ieo 16 aaoa?iceaioiuo iineoaey aaia. Ai anao neo/ayo aeeaaiinoeee ioeiaenoeeaeica, ca eneeth/aieai iaeiie naiuee, ana aa?aiaiiinoe auee i?a?aaiu. A 5-oe iieoeioi?iaoeaiuo naiueyo, aaea ?ene aue 50:50, eie auei i?eiyoi ?aoaiea i i?a?uaaiee aa?aiaiiinoe. Oaeei ia?acii, ana auoaeceiaeaiiia iiaeoaa?aeaeaao, /oi a ianoiyuaa a?aiy yooaeoeaiie i?ioeeaeoeeie IA yaeyaony iaaeeei-aaiaoe/aneia eiinoeueoe?iaaiea e aei?iaeiaay aeeaaiinoeea n eniieueciaaieai iieaeoey?ii-aaiaoe/aneeo iaoiaeia. Iaeaieaa yooaeoeaiui yaeyaony eiinoeueoe?iaaiea naiuee e ieaie?iaaiea aei?iaeiaie aeeaaiinoeee aei ianooieaiey aa?aiaiiinoe, /oi niinianoaoao naiaa?aiaiiiio e iaeneiaeueiiio eniieueciaaieth anao iaoiaeia aei?iaeiaie aeeaaiinoeee. Ii oaia aeenna?oaoeee iioaeeeiaaii 11 iao/iuo ?aaio. A manuscript of dissertation for a Candidate’s degree of medical sciences on Speciality 03.00.15 – genetics. Ukrainian Scientific Centre of Hygiene. Kyiv, 1999. In thesises the comparative characteristic of clinical manifestation of pulmonary and gastrointestinal diseases depending on genotype of 111 children CF patients (age range from 1 month to 15 years old) is exposed. According to the results of DNA analysis the gen-mutations CFTR protein: F508-57,2%; R553X-0,45%; G551D-0,45% are revealed. The children with disorders were divided into three genotypical groups. The first group – with genotype F508/F508 (39,6%), the second group – with F508/X (33,4%) and the third on – with X/X (27%). The physical development of children is evaluated depending on their genotype. The author offers to use these indices for assessment of severity of disorder and forecasting of its course. The scheme of genetic counselling and prenatal diagnosis is optimised, allowing to rise considerably the diagnostical infomativeness of the families with high degree of risk of CF (to 95,5%), that is of great medical and social importance. 11 scientific articles on the subject of dissertation were published.

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