Phát hiện đột biến gen CYP21A2 ở bệnh nhân tăng sản thượng thận bẩm sinh

TAP CHl NGHliN CO'U Y HQC

PHAT HIEN DOT BI^N GEN CYP21A2 (y BENH NHAN • • •

TANG SAN THU'Q'NG THAN BAM SINH

Trln Vdn Khdnh, LO Thj Phu'ang, Trln Huy Thjnh, Ta Thdnh Vdn

Trwdng Dai hpc Y Hd Npi

Tdng sdn thugng thdn bim sinh (TSTTBS) do thiiu hut enzyme 21-hydroxylase Id mdt tmng cdc bdnh di

tmyin ldn nhiim sic thi thudng phd biin nhit. Bdnh gdy ndn do ddt biin gen CYP21A2. Phdt hidn ddt biin

gen CYP21A2 ddng vai trd quan trpng tmng chin dodn bdnh. phdt hidn ngudi Idnh mang gen, chin dodn vd

diu trj tmdc sinh bdnh TSTTBS. Nghidn cdu nhim phdt hidn cde ddt biin gen CYP21A2 gdy bdnh

TSTTBS. Kit qud cho thiy cd 5 bdnh nhdn dd dwgc phdt hidn ddt biin bao gdm: 1/5 bdnh nhdn cd ddt biin

xda dopn Idn, 2/5 bdnh nhdn ed ddt biin In2 A/C-*G. 1/5 bdnh nhdn cd ddt biin I172N vd 1/5 bdnh nhdn c6

ddt biin R356W. Kit ludn: Cdc ddt biin cua gen CYP21A2 gdy bdnh TSTTBS dd dwgc phdt hidn thdnh cdng

bing ky thudt gidi trinh tw gen vd ky thudt MLPA.

TLF khda: Tdng sdn thup'ng th^n bim sinh; dft biln gen CYP21A2

I. DAT VAN O^

Tdng san thupng thdn bim sinh (TSTTBS)

Id bOnh ly do sy thidu hyt mpt trong ba enzym

cin thiet eho qud trinh tdng hpp hormon vd

thuang thdn: 21-hydroxylase (21-OH); 11|3-

hydroxylase vd 3(3-hydroxysteroid dehydro￾genase, trong dd sy thieu hyt ezym 21-OH

chiem 90 - 95% cdc trudng hpp [7]. TSTTBS

Id bOnh di truyen ldn trOn nhidm sic the

thudng phd bien nhit, do ddt bidn gen quy

djnh tdng hpp protein 21-OH (CYP21A2) - en￾zym xue tdc qud trinh tdng hpp Cortisol [2, 5].

OOt bidn gen CYP21A2 din ddn sy mit

hodc thieu hyt enzym 21-OH, gilm ho$c

khOng dupe tdng hpp dupc Cortisol nhung

tdng tdng hpp testosterone. Bidu hiOn Idm

sdng cua bOnh Id suy thupng thdn clp, nam

hda don thuin d tre gdi vd ddy thl sdm d trO

trai. Tuy miPC dO thidu hyt enzym 21-OH,

TSTTBS gdm 3 thd ldm sdng: thd ed didn mit

mudi (Salt-w/asting-SW), thd ed didn nam hda

dan thuin (Simple virilizing-SV) vd thd khOng

cd dien (non-classic) [4, 6]; trong dd thd cd

dien mit mudi Id thd hay gdp nhit, enzym 21 -

OH bj thidu hyt hodn todn (0%) ho$e ed rit it

bOnh nhdn thudng bidu hiOn suy thupng thdn,

gilm natri mdu, tdng kali mdu, tdng renin mdu,

sdc giam the tieh ed the xay ra vd din den tii￾vong [9].

Ngdy nay, gen CYP21A2 di dupe phdt

hiOn vd giai trinh ty. Viec phdn tich dOt bien

gen CYP21A2 ed vai trd quan trpng xdc djnh

bOnh khi ehln dodn Idm sdng vd hda sinh gdp

nhidu khd khdn. Han nO-a ehln dodn bOnh

bing xOt nghiOm sinh hpc phdn tir gdp phin

phdn logi thd ldm sdng TSTTBS, giup djnh

hudng viOc eh? djnh didu tri bing liOu phdp

hormon thay thd sudt ddi vd Id ca sd eua tu￾vln di truydn, ehln dodn vd dieu tri trudc sinh

bOnh TSTTBS. NghiOn cu-u ndy dupe thyc

hiOn nhim myc tiOu: nghiOn ciru phdt hiOn

dot bidn gen CYP21A2 gdy bOnh TSTTBS

bing ky thudt giai trinh ty gen vd MLPA.

II. 06l TU'gNG VA PHU'ONG PHAP

1. Ddi tu'p'ng

5 bOnh nhdn di dwgc ehln dodn mie bOnh

TSTTBS do thieu enzym 21 - OH dya vdo cdc

tiOu chuln Idm sdng vd hda sinh tai bOnh vifn

Nhi Trung uang.

148 TCNCYH 78 (1) - 2012