摘要
目的:对一个家族遗传性多指并指畸形进行临床及分子遗传学分析。方法:对1个孕期提示胎儿多指并指畸形的家系行产前诊断。孕24+5周于泉州市妇幼保健院·儿童医院产前诊断行羊水穿刺,利用染色体核型分析对胎儿行染色体异常诊断。同时,利用全外显子组测序(whole exome sequencing,WES)分析胎儿微小变异。此外,通过实时荧光定量聚合酶链反应(quantitative real time polymerase chain reaction,qPCR)进行微缺失/微重复验证。结果:胎儿染色体核型结果未见异常。胎儿WES检测结果显示在7q36.3区域存在一个803.7 kb片段重复(seq[GRCh37]7q36.3(155865332_156669022)×3),包含RNF32基因以及LMBR1基因的2~17号外显子。依据美国医学遗传学与基因组学学会(the American College of Medical Genetics and Genomics,ACMG)指南,该重复判读为致病性。父母qPCR验证提示,该重复遗传自具有同样表型的父亲。结论:明确了7q36.3微重复为胎儿多指并指畸形遗传病因,该重复可能导致了三指节拇指-多并指/趾畸形综合征,其中LMBR1为其主要起效基因。
Objective:To conduct clinical and molecular genetic analysis in a Chinese family with familial polysyndactyly.Methods:A pregnant woman with fetal polysyndactyly was enrolled in this study,amniocentesis was performed at Quanzhou Women′s and Children′s Hospital for prenatal diagnosis at the gestational age of 24+5 weeks.Chromosomal karyotype analysis was performed to reveal fetal chromosomal abnormalities.Subsequently,whole exome sequencing(WES)was carried out to analyze sequence variations.Quantitative real time polymerase chain reaction(qPCR)was use to confirm the detected microdeletion/microduplication.Results:The fetal chromosome karyotype results elicited a normal karyotype result.However,WES demonstrated an 803.7 kb fragment duplication(seq[GRCh37]7q36.3(155865332_156669022)×3)in the 7q36.3 region in the fetus,which covering RNF32 and LMBR1(exon 2 to exon 17).According to the American College of Medical Genetics and Genomics(ACMG)guidelines,the 7q36.3 duplication was interpreted as pathogenic copy number variants.The subsequent qPCR verification indicated that the duplication was inherited from the father who had similar clinical phenotype.Conclusions:Our findings further confirm that 7q36.3 microduplication is the genetic cause for fetal polysyndactyly,which may lead to triphalangeal thumb-polysyndactyly syndrome,LMBR1 may be the main effector gene.
作者
庄建龙
许伟雄
江矞颖
ZHUANG Jian-long;XU Wei-xiong;JIANG Yu-ying(Prenatal Diagnosis Center,Quanzhou Women′s and Children′s Hospital,Quanzhou 362000,Fujian Province,China;Department of Laboratory,The 910 Hospital of the Joint Logistics and Support Force of the Chinese PLA,Quanzhou 362000,Fujian Province,China)
出处
《国际生殖健康／计划生育杂志》
CAS
2024年第4期284-288,共5页
Journal of International Reproductive Health/Family Planning
基金
泉州市科技计划项目(2023NS068)
福建省卫健委青年科研项目(2020QNB045)。
