Bardet-Biedl综合征2例胎儿的产前表型及遗传学分析  

Prenatal phenotype and genetic analysis of two fetuses with Bardet-Biedl syndrome

作　　者：张令怡 张志刚 王兴光 李艳艳 Zhang Lingyi;Zhang Zhigang;Wang Xingguang;Li Yanyan(Cangzhou People′s Hospital,Cangzhou,Hebei 061000,China)

机构地区：[1]沧州市人民医院,沧州061000

出　　处：《中华医学遗传学杂志》2025年第2期226-231,共6页Chinese Journal of Medical Genetics

基　　金：沧州市科技支撑计划(204106024)。

摘　　要：目的对2例产前超声发现多指(趾)和肾脏异常的胎儿进行基因检测,以明确其遗传学病因。方法以2021年在沧州市人民医院因产前超声检查发现异常并引产的2例胎儿作为研究对象,采集引产胎儿组织及其孕妇夫妇的外周血样,提取基因组DNA,进行家系全外显子组测序(Trio-WES)。用定量PCR法验证基因的外显子缺失。本研究通过了沧州市人民医院的伦理学审查(批准号:K2020-049)结果胎儿1双手双足存在轴后型多指(趾),双肾稍大且肾实质回声增强;胎儿2存在双手多指,双肾增大,肾实质回声增强。Trio-WES检测提示胎儿1携带BBS1基因c.1339G>A致病性变异和染色体11q13.2区426 bp的杂合缺失,涉及BBS1基因的第10~11外显子。上述变异分别遗传自孕妇及丈夫。胎儿2携带BBS10基因c.539G>A致病性变异和c.49G>A可能致病性变异,分别遗传自孕妇及其丈夫,其中c.49G>A变异既往未见报道。结论本研究确诊了2例罕见的Bardet-Biedl综合征胎儿,扩展了该病的突变谱,对指导两个家庭的再生育提供了依据,同时证实了Trio-WES检测拷贝数变异的可靠性。ObjectiveTo carry out genetic testing on two fetuses with prenatal ultrasound finding of polydactyly and renal abnormalities to determine the underlying causes.MethodsTwo fetuses with structural abnormalities detected by prenatal ultrasound at Cangzhou People′s Hospital in 2021 were selected as the study subjects.Genomic DNA was extracted from the muscle tissue of the abortus and peripheral blood samples from both parents.Whole-exome sequencing(WES)was conducted on the trio to detect the genetic variants.Quantitative PCR was used to validate the exonic deletions.This study has been approved by the Ethics Committee of Cangzhou People′s Hospital(Ethics No.K2020-049).ResultsPrenatal ultrasound revealed postaxial polydactylies of fingers and toes and slightly enlarged kidneys with increased echogenicity in fetus 1,along with polydactyly of both hands,enlarged kidneys,and enhanced echogenicity of renal parenchyma in fetus 2.Trio-WES analysis revealed that fetus 1 has harbored a pathogenic c.1339G>A variant of the BBS1 gene,along with a heterozygous 426 bp deletion in the 11q13.2 region,which was unreported previously.The deletion has involved exons 10 and 11 of the BBS1 gene.The two variants were inherited from its mother and father,respectively.Fetus 2 was found to harbor a pathogenic c.539G>A variant and a likely pathogenic c.49G>A variant of the BBS10 gene,which were inherited from its mother and father,respectively.The c.49G>A variant has not been documented in databases and the literature.ConclusionTwo rare fetuses with Bardet-Biedl syndrome have been diagnosed.Above finding has expanded the mutational spectrum of this syndrome and has important implications for genetic counseling for the affected families.

关 键 词：Bardet-Bied综合征 BBS1基因 BBS10基因 家系全外显子组测序 

分 类 号：R714.5[医药卫生—妇产科学]