中华妇产科杂志
中華婦產科雜誌
중화부산과잡지
CHINESE JOUNAL OF OBSTETRICS AND GYNECOLOGY
2014年
12期
893-898
,共6页
吴晓丽%符芳%李茹%潘敏%韩瑾%甄理%杨昕%张永玲%李发涛
吳曉麗%符芳%李茹%潘敏%韓瑾%甄理%楊昕%張永玲%李髮濤
오효려%부방%리여%반민%한근%견리%양흔%장영령%리발도
心脏缺损,先天性%微阵列分析%超声心动描记术%超声检查,产前%DNA拷贝数变异%染色体缺失
心髒缺損,先天性%微陣列分析%超聲心動描記術%超聲檢查,產前%DNA拷貝數變異%染色體缺失
심장결손,선천성%미진렬분석%초성심동묘기술%초성검사,산전%DNA고패수변이%염색체결실
Heart defects,congenital%Microarray analysis%Echocardiography%Ultrasonography,prenatal%DNA copy number variations%Chromosome deletion
目的 探讨全基因组高分辨率染色体微阵列分析(CMA)技术对超声心动图检查提示为先天性心脏病(CHD)的胎儿进行遗传病因学诊断的临床价值.方法 收集2012年1月至2014年1月在广州医科大学附属广州市妇女儿童医疗中心就诊并接受侵入性产前诊断的176例超声心动图检查提示为CHD胎儿的临床资料,在其中158例染色体核型分析结果正常的CHD胎儿中,有88例(50.0％,88/176)胎儿进行了CMA检测.同时收集所有CHD胎儿的父母外周血标本,用于不明确临床意义的拷贝数变异(vOUS)的协助诊断.88例行CMA检测胎儿分为两组,68例单纯心脏结构异常的CHD胎儿为单纯心脏结构异常组;20例合并心外结构异常的CHD胎儿为合并心外结构异常组,对两组胎儿的CHD表型进行分类,对检出的染色体拷贝数变异(CNV)性质按致病性CNV、VOUS及良性CNV进行分类.结果 (1)88例行CMA检测的胎儿中,单一类型CHD胎儿共58例(66％,58/88),复合类型CHD胎儿共30例(34％,30/88).其中,单纯心脏结构异常组单一类型CHD胎儿45例,其致病性CNV检出率为11％(5/45);复合类型CHD胎儿23例,其致病性CNV检出率为17％ (4/23).合并心外结构异常组单一类型CHD胎儿13例,其致病性CNV检出率为5/13;复合类型CHD胎儿7例,其致病性CNV检出率为0.(2)88例行CMA检测的CHD胎儿致病性CNV的总检出率为16％(14/88),其中单纯心脏结构异常组致病性CNV检出率为13％(9/68),合并心外结构异常组致病性CNV检出率为25％(5/20),两组比较,差异无统计学意义(P=0.206);单一类型CHD胎儿致病性CNV检出率为17％(10/58),复合类型CHD胎儿致病性CNV检出率为13％ (4/30),两者比较,差异无统计学意义(P=0.867).(3)176例CHD胎儿中,共有18例染色体核型分析结果异常,发生率为10.2％(18/176),余158例胎儿染色体核型分析结果正常.(4)88例胎儿进行了CMA检测,有8例胎儿CNV检测,结果为VOUS,对其父母的外周血进行CMA检测结果显示,其中5例胎儿CNV遗传自父母,为良性CNV;其余3例(3％,3/88)CNV的临床意义仍然无法明确.14例(16％)胎儿CNV结果为致病性CNV.结论 对染色体核型分析结果正常的CHD胎儿进行CMA检测,能额外发现部分致病性CNV;推荐在产前诊断的CHD胎儿中应用全基因组CMA技术作为常规分子诊断方法,更有助于遗传咨询中正确评估胎儿的预后.
目的 探討全基因組高分辨率染色體微陣列分析(CMA)技術對超聲心動圖檢查提示為先天性心髒病(CHD)的胎兒進行遺傳病因學診斷的臨床價值.方法 收集2012年1月至2014年1月在廣州醫科大學附屬廣州市婦女兒童醫療中心就診併接受侵入性產前診斷的176例超聲心動圖檢查提示為CHD胎兒的臨床資料,在其中158例染色體覈型分析結果正常的CHD胎兒中,有88例(50.0％,88/176)胎兒進行瞭CMA檢測.同時收集所有CHD胎兒的父母外週血標本,用于不明確臨床意義的拷貝數變異(vOUS)的協助診斷.88例行CMA檢測胎兒分為兩組,68例單純心髒結構異常的CHD胎兒為單純心髒結構異常組;20例閤併心外結構異常的CHD胎兒為閤併心外結構異常組,對兩組胎兒的CHD錶型進行分類,對檢齣的染色體拷貝數變異(CNV)性質按緻病性CNV、VOUS及良性CNV進行分類.結果 (1)88例行CMA檢測的胎兒中,單一類型CHD胎兒共58例(66％,58/88),複閤類型CHD胎兒共30例(34％,30/88).其中,單純心髒結構異常組單一類型CHD胎兒45例,其緻病性CNV檢齣率為11％(5/45);複閤類型CHD胎兒23例,其緻病性CNV檢齣率為17％ (4/23).閤併心外結構異常組單一類型CHD胎兒13例,其緻病性CNV檢齣率為5/13;複閤類型CHD胎兒7例,其緻病性CNV檢齣率為0.(2)88例行CMA檢測的CHD胎兒緻病性CNV的總檢齣率為16％(14/88),其中單純心髒結構異常組緻病性CNV檢齣率為13％(9/68),閤併心外結構異常組緻病性CNV檢齣率為25％(5/20),兩組比較,差異無統計學意義(P=0.206);單一類型CHD胎兒緻病性CNV檢齣率為17％(10/58),複閤類型CHD胎兒緻病性CNV檢齣率為13％ (4/30),兩者比較,差異無統計學意義(P=0.867).(3)176例CHD胎兒中,共有18例染色體覈型分析結果異常,髮生率為10.2％(18/176),餘158例胎兒染色體覈型分析結果正常.(4)88例胎兒進行瞭CMA檢測,有8例胎兒CNV檢測,結果為VOUS,對其父母的外週血進行CMA檢測結果顯示,其中5例胎兒CNV遺傳自父母,為良性CNV;其餘3例(3％,3/88)CNV的臨床意義仍然無法明確.14例(16％)胎兒CNV結果為緻病性CNV.結論 對染色體覈型分析結果正常的CHD胎兒進行CMA檢測,能額外髮現部分緻病性CNV;推薦在產前診斷的CHD胎兒中應用全基因組CMA技術作為常規分子診斷方法,更有助于遺傳咨詢中正確評估胎兒的預後.
목적 탐토전기인조고분변솔염색체미진렬분석(CMA)기술대초성심동도검사제시위선천성심장병(CHD)적태인진행유전병인학진단적림상개치.방법 수집2012년1월지2014년1월재엄주의과대학부속엄주시부녀인동의료중심취진병접수침입성산전진단적176례초성심동도검사제시위CHD태인적림상자료,재기중158례염색체핵형분석결과정상적CHD태인중,유88례(50.0％,88/176)태인진행료CMA검측.동시수집소유CHD태인적부모외주혈표본,용우불명학림상의의적고패수변이(vOUS)적협조진단.88례행CMA검측태인분위량조,68례단순심장결구이상적CHD태인위단순심장결구이상조;20례합병심외결구이상적CHD태인위합병심외결구이상조,대량조태인적CHD표형진행분류,대검출적염색체고패수변이(CNV)성질안치병성CNV、VOUS급량성CNV진행분류.결과 (1)88례행CMA검측적태인중,단일류형CHD태인공58례(66％,58/88),복합류형CHD태인공30례(34％,30/88).기중,단순심장결구이상조단일류형CHD태인45례,기치병성CNV검출솔위11％(5/45);복합류형CHD태인23례,기치병성CNV검출솔위17％ (4/23).합병심외결구이상조단일류형CHD태인13례,기치병성CNV검출솔위5/13;복합류형CHD태인7례,기치병성CNV검출솔위0.(2)88례행CMA검측적CHD태인치병성CNV적총검출솔위16％(14/88),기중단순심장결구이상조치병성CNV검출솔위13％(9/68),합병심외결구이상조치병성CNV검출솔위25％(5/20),량조비교,차이무통계학의의(P=0.206);단일류형CHD태인치병성CNV검출솔위17％(10/58),복합류형CHD태인치병성CNV검출솔위13％ (4/30),량자비교,차이무통계학의의(P=0.867).(3)176례CHD태인중,공유18례염색체핵형분석결과이상,발생솔위10.2％(18/176),여158례태인염색체핵형분석결과정상.(4)88례태인진행료CMA검측,유8례태인CNV검측,결과위VOUS,대기부모적외주혈진행CMA검측결과현시,기중5례태인CNV유전자부모,위량성CNV;기여3례(3％,3/88)CNV적림상의의잉연무법명학.14례(16％)태인CNV결과위치병성CNV.결론 대염색체핵형분석결과정상적CHD태인진행CMA검측,능액외발현부분치병성CNV;추천재산전진단적CHD태인중응용전기인조CMA기술작위상규분자진단방법,경유조우유전자순중정학평고태인적예후.
Objective To explore the clinical value of genome-wide high resolution chromosomal microarray analysis (CMA) in etiological study of fetuses with congenital heart disease (CHD) diagnosed by fetal echocardiography.Methods A total of 176 fetuses diagnosed CHD by fetal echocardiography were analyzed,and invasive prenatal diagnosis was performed at Guangzhou Women and Children's Medical Center from January 2012 to January 2014.Among them,158 fetuses were proved to have normal karyotype,and 88 fetuses (50.0％,88/176) underwent CMA testing.The parental blood specimens were also collected for assisting the diagnosis of variants of uncertain clinical significance (VOUS).The 88 fetuses were divided into two groups:isolated CHD (n=68) and CHD with extra-cardiac structural abnormalities (n=20).The phenotypes of the two groups were subclassified.Copy number variations (CNV) were classified as benign CNV,pathogenic CNV (pCNV) or VOUS.Results (1) 58 fetuses (66％,58/88) were with simple CHD and 30 fetuses were with complicated CHD (34％,30/88).In the 45 fetuses with isolated and simple CHD,the pCNV detection rate was 11％ (5/45).In the 23 fetuses with isolated and complicated CHD,the pCNV detection rate was 17％ (4/23).In the 13 fetuses with simple CHD and extra-cardiac structural abnormalities,the pCNV detection rate was 5/13.In the 7 fetuses with complicated CHD and extra-cardiac structural abnormalities,the pCNV detection rate was 0.(2) The total detection rate for pCNV detection was 16％ (14/88) in the 88 fetuses.The pCNV detection rates for isolated CHD and CHD with extra-cardiac structural abnormalities were 13％ (9/68) and 25％ (5/20),respectively (P＞0.05).The pCNV detection rates for simple and complicated CHD were 17％ (10/58) and 13％ (4/30),respectively (P＞0.05).(3) Eighteen fetuses (10.2％,18/176) had abnormal karyotype results.(4) CMA test was performed in 88 fetuses.CNV detected in 8 fetuses were classified as VOUS initially.After parental microarray analysis,CNV in 5 fetuses were inherited and interpreted as benign.CNV in the other 3 fetuses (3％,3/88) were remained unknown significance.CNV in 14 fetuses (16％) were interpreted as pCNV.Conclusions In fetuses with CHD and normal karyotype,the application of CMA could increase the detection rate of pCNV.Genome-wide CMA could be used as a regular tool in the prenatal diagnosis of fetuses with CHD and normal karyotype.This technology may benefit evaluation of fetal prognosis in prenatal genetic counselling.
