四例Jacobsen综合征胎儿的产前诊断

Prenatal diagnosis of Jacobsen syndrome： analysis of four cases

目的探讨染色体微阵列分析技术在产前诊断Jacobsen综合征中的价值。方法2014年至2016年，因胎儿存在先天性心脏畸形于南方医科大学附属深圳市妇幼保健院行胎儿染色体核型分析和染色体微阵列分析检查的孕妇中，共诊断4例胎儿Jacobsen综合征，纳入研究。留取3例胎儿羊水标本和1例胎儿组织标本以及4例胎儿父母外周血标本。对3例羊水标本及4例胎儿父母外周血标本进行G显带染色体核型分析，对3例胎儿羊水标本及1例胎儿组织标本进行染色体微阵列分析。对染色体微阵列分析发现的异常结果通过多重连接依赖探针扩增技术进行验证。结果（1）产前超声：胎儿1单腔心、大动脉转位；胎儿2单脐动脉、双上腔静脉；胎儿3主动脉严重缩窄并室间隔缺损；胎儿4颈项透明层0．27cm，左心发育不良综合征。（2）染色体核型分析：3例胎儿羊水标本染色体核型分析结果分别为46，XY,del（11）（q23．3）、46，XX，de1（11）（q23．3）和46，XX，de1（11）（q23）。（3）染色体微阵列分析结果：4例结果分别为arr[GRCh37]11q24．1q25（121872273—134934196）×1，缺失13．062Mb；arr[GRCh37]11q24．1q25（121325694—134937416）×1，缺失13．611Mb；arr[GRCh37]11q23．3q25（118977029—134937416）×1，缺失15．960Mb；arr[GRCh37111q24．1q24．3（123144040—130308335）×1，缺失7．164Mb。4例胎儿父母外周血染色体核型分析均无异常发现，提示4例胎儿染色体异常均为新发变异。4例染色体微阵列分析发现的异常结果均得到多重连接依赖探针扩增技术验证。结论对于产前超声提示存在先天性心脏畸形的胎儿要警惕Jacobsen综合征的可能；染色体微阵列分析技术能够明确诊断Jacobsen综合征及确定该类患儿染色体缺失的区域及大小。

Objective To investiget the value of chromosome microarray analysis （CMA） in prenatal diagnosis of Jacobsen syndrome. Methods Among all gravidas who received karyotype analysis and CMA because of fetal congenital cardiac abnormalities in Shenzhen Maternity ＆ Child Healthcare Hospital Affiliated to Southern Medical University from 2014 to 2016, four were diagnosed with fetal Jacobsen syndrome and enrolled in this study. Three amniotic fluid and one fetal tissue samples were collected. Peripheral blood specimens were collected from parents of these fetuses. Amniotic fluid samples and peripheral blood specimens were analyzed by karyotype analysis. CMA was performed to analyze amniotic fluid and fetal tissue samples. Multiplex ligation-dependent probe amplification was used to verify abnormal results revealed by CMA. Results （1） Prenatal ultrasound results： Fetus 1 was complicated with monocardian and transposition of the great arteries, fetus 2 with single umbilical artery and double superior vena cava, fetus 3 with severe constricted aorta and ventricular septal defect and fetus 4 with hypoplastic left heart syndrome and presented with a nuchal translucency of 0.27 cm. （2） Karyotyping results of the three amniotic fluid samples were 46,XY, del（11）（q23.3）, 46,XX,del（11）（q23.3） and 46,XX,del（11）（q23）, respectively. （3） CMA results of the four fetuses were arr[GRCh37]llq24.1q25（121 872 273-134 934 196）× 1 （13.062 Mb）, arr[GRCh37]11q24.1q25（121 325 694-134 937 416）× 1 （13.611 Mb）, arr[GRCh37]11q23.3q25 （118 977 029-134 937 416）× 1 （15.960 Mb） and arr[GRCh37]11q24.1q24.3（123 144 040-130 308 335）× 1 （7.164 Mb）, respectively. All chromosomal aberrations in these fetuses were de novo as no abnormalities were found in their parents through karyotyping. All abnormal CMA results were confirmed by multiplex ligationdependent probe amplification. Conclusions Jacobsen syndrome should be considered when fetuses are diagnosed with congenital cardiac abnormalities by ultrasound. CMA can be used to accurately diagnose Jacobsen syndrome and determine the region and size of chromosome deletion.