CAJ | 학술논문

目的通过回顾遗传性耳聋家庭产前诊断的临床实践,总结耳聋产前诊断的相关流程策略与经验.方法 2005年7月至2011年4月,213个耳聋家庭参加研究.其中,205个家庭已生育1个耳聋患儿,除1个家庭妻子为听力正常个体而丈夫为耳聋患者外,其余204个家庭的父母均听力正常；8个家庭为首次生育,包括2个耳聋夫妇家庭.除了1个家庭是经家系研究确定为POU3F4c.647G ＞A杂合突变导致X伴性耳聋外,其余212个家庭均行常见耳聋基因检测,包括GJB2、SLC26A4分析和线粒体基因(mtDNA) 12S rRNA检测,明确分子病因和后代再发风险.接受产前诊断时,母亲妊娠11 ～30周,根据妊娠时间,行适当的产前诊断取材并提取胎儿DNA,测定胎儿基因型,预测胎儿听力状态.结果后代再发风险为25％的家庭共209个,其中,再生育家庭204个,先证者均为GJB2或SLC26A4纯合或复合突变,父母均为相同基因GJB2或SLC26A4突变携带者；5个首次生育家庭中的夫妇同为GJB2或SLC26A4突变携带者.后代再发风险为50％的家庭共3个,1个家庭先证者及父亲均为SLC26A4复合突变,母亲为SLC26A4突变携带者；1个家庭妻子为POU3F4突变携带者；1个家庭为耳聋夫妇,丈夫为SLC26A4复合突变,妻子同时携带mtDNA A1555G突变和SLC26A4杂合突变.后代再发风险为100％的家庭1个,夫妇均为GJB2纯合或复合突变,但妻子从精子库选择健康人精子,人工受精后怀孕.产前诊断结果显示:213个家庭共行产前诊断226例次(11个家庭进行了2次产前诊断,1例家庭行3次产前诊断),180例次检测结果显示胎儿仅携带一个父系或母系突变,或未携带任何已知突变,该180个胎儿均已出生,随访听力均正常；46例次检测结果显示胎儿与先证者基因型相同,或同时携带了父母的突变,父母自愿选择终止妊娠.结论耳聋基因诊断结合产前诊断可以有效预防耳聋家庭生育或再生育聋儿,严谨规范的流程与策略是耳聋产前诊断临床安全顺利实施的保证. 目的通過迴顧遺傳性耳聾傢庭產前診斷的臨床實踐,總結耳聾產前診斷的相關流程策略與經驗.方法 2005年7月至2011年4月,213箇耳聾傢庭參加研究.其中,205箇傢庭已生育1箇耳聾患兒,除1箇傢庭妻子為聽力正常箇體而丈伕為耳聾患者外,其餘204箇傢庭的父母均聽力正常；8箇傢庭為首次生育,包括2箇耳聾伕婦傢庭.除瞭1箇傢庭是經傢繫研究確定為POU3F4c.647G ＞A雜閤突變導緻X伴性耳聾外,其餘212箇傢庭均行常見耳聾基因檢測,包括GJB2、SLC26A4分析和線粒體基因(mtDNA) 12S rRNA檢測,明確分子病因和後代再髮風險.接受產前診斷時,母親妊娠11 ～30週,根據妊娠時間,行適噹的產前診斷取材併提取胎兒DNA,測定胎兒基因型,預測胎兒聽力狀態.結果後代再髮風險為25％的傢庭共209箇,其中,再生育傢庭204箇,先證者均為GJB2或SLC26A4純閤或複閤突變,父母均為相同基因GJB2或SLC26A4突變攜帶者；5箇首次生育傢庭中的伕婦同為GJB2或SLC26A4突變攜帶者.後代再髮風險為50％的傢庭共3箇,1箇傢庭先證者及父親均為SLC26A4複閤突變,母親為SLC26A4突變攜帶者；1箇傢庭妻子為POU3F4突變攜帶者；1箇傢庭為耳聾伕婦,丈伕為SLC26A4複閤突變,妻子同時攜帶mtDNA A1555G突變和SLC26A4雜閤突變.後代再髮風險為100％的傢庭1箇,伕婦均為GJB2純閤或複閤突變,但妻子從精子庫選擇健康人精子,人工受精後懷孕.產前診斷結果顯示:213箇傢庭共行產前診斷226例次(11箇傢庭進行瞭2次產前診斷,1例傢庭行3次產前診斷),180例次檢測結果顯示胎兒僅攜帶一箇父繫或母繫突變,或未攜帶任何已知突變,該180箇胎兒均已齣生,隨訪聽力均正常；46例次檢測結果顯示胎兒與先證者基因型相同,或同時攜帶瞭父母的突變,父母自願選擇終止妊娠.結論耳聾基因診斷結閤產前診斷可以有效預防耳聾傢庭生育或再生育聾兒,嚴謹規範的流程與策略是耳聾產前診斷臨床安全順利實施的保證.
목적 통과회고유전성이롱가정산전진단적림상실천,총결이롱산전진단적상관류정책략여경험.방법 2005년7월지2011년4월,213개이롱가정삼가연구.기중,205개가정이생육1개이롱환인,제1개가정처자위은력정상개체이장부위이롱환자외,기여204개가정적부모균은력정상；8개가정위수차생육,포괄2개이롱부부가정.제료1개가정시경가계연구학정위POU3F4c.647G ＞A잡합돌변도치X반성이롱외,기여212개가정균행상견이롱기인검측,포괄GJB2、SLC26A4분석화선립체기인(mtDNA) 12S rRNA검측,명학분자병인화후대재발풍험.접수산전진단시,모친임신11 ～30주,근거임신시간,행괄당적산전진단취재병제취태인DNA,측정태인기인형,예측태인은력상태.결과 후대재발풍험위25％적가정공209개,기중,재생육가정204개,선증자균위GJB2혹SLC26A4순합혹복합돌변,부모균위상동기인GJB2혹SLC26A4돌변휴대자；5개수차생육가정중적부부동위GJB2혹SLC26A4돌변휴대자.후대재발풍험위50％적가정공3개,1개가정선증자급부친균위SLC26A4복합돌변,모친위SLC26A4돌변휴대자；1개가정처자위POU3F4돌변휴대자；1개가정위이롱부부,장부위SLC26A4복합돌변,처자동시휴대mtDNA A1555G돌변화SLC26A4잡합돌변.후대재발풍험위100％적가정1개,부부균위GJB2순합혹복합돌변,단처자종정자고선택건강인정자,인공수정후부잉.산전진단결과현시:213개가정공행산전진단226례차(11개가정진행료2차산전진단,1례가정행3차산전진단),180례차검측결과현시태인부휴대일개부계혹모계돌변,혹미휴대임하이지돌변,해180개태인균이출생,수방은력균정상；46례차검측결과현시태인여선증자기인형상동,혹동시휴대료부모적돌변,부모자원선택종지임신.결론 이롱기인진단결합산전진단가이유효예방이롱가정생육혹재생육롱인,엄근규범적류정여책략시이롱산전진단림상안전순리실시적보증.
Objective To summarize the workflow,strategy and experience of prenatal genetic test for deafness based on the 6-year clinical practice.Methods There were 213 famihes who received prenatal test from 2005 to 2011.Among the 213 families,205 families had had one deaf child,including 204 couples with normal hearing and one couple of the deaf husband and normal wife,8 families including 6 couples with normal hearing and 2 deaf couples,had no child before test. Genomic and mitochondrial DNA of each subject was extracted from whole blood.The etiology and recurrent risks in 212 families were confirmed by means of the genetic test of GJB2,SLC26A4 and mtDNA 12sRNA,but one family carried POU3F4 c.647G ＞ A heterozygous mutation causing X-linked hereditary hearing impairment confirmed by pedigree study.The prenatal test was carried out during the pregnancy of all mothers from 11 to 30 weeks,and the following genetic information and counseling were supplied based on the results.Results The recurrent risk was 25％in 209 families,including 204 families with one deaf child and 5 families without child,among which all couples were GJB2 or SLC26A4 mutation carriers and deaf children were caused by homozygous or compound GJB2/SLC26A4 mutations; The recurrent risk was 50％ in 3 families,the father and his child in one family had compound SLC26A4 mutations and the mother with heterozygous SLC26A4 mutation,the wife had POU3F4 c.647G ＞ A heterozygous mutation in another one family,and the husband with compound SLC26A4 mutations and the wife with mtDNA A1555G mutation and heterozygous SLC26A4 mutation simultaneously happened in the rest one family; The recurrent risk was 100％ in one family of the deaf couple who were both found to carry homozygous or compound GJB2 mutations,and the deaf wife got pregnant by artificial insemination with the sperm from the local Human Sperm Bank.226 times of prenatal test were applied in all 213 families that 11 families of them received prenatal test twice,and one family received three times. 46 times of prenatal testing showed that the fetuses carried parental mutations simultaneously or the same mutations with probands ; while 180 times of prenatal test showed that the fetuses carried only one parental mutation or did not carry any mutation from parents.The following visit showed that all of these 180 families had given birth to babies who were all revealed to have normal hearing by new born hearing screening test.Conclusions Prenatal diagnosis for deafness assisted by genetic test can provide efficient information about offspring's hearing condition,and the normative workflow and precise strategy highy guarantee the safe and favorable implementation of prental diagnosis.