鳃裂眼面综合征一个家系的遗传学分析暨文献复习  

Genetic analysis of a Chinese pedigree affected with Branchio-oculo-facial syndrome and a literature review

作　　者：李珂[1] 孙恒青 郭煜[2] 孙阁阁 段会坤 孔祥东[1] 刘宁[1] Li Ke;Sun Hengqing;Guo Yu;Sun Gege;Duan Huikun;Kong Xiangdong;Liu Ning(Genetic and Prenatal Diagnosis Center,Department of Obstetrics and Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Department of Ultrasonography,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院妇产医学部遗传与产前诊断中心,郑州450052 [2]郑州大学第一附属医院超声科,郑州450052

出　　处：《中华医学遗传学杂志》2024年第9期1084-1089,共6页Chinese Journal of Medical Genetics

摘　　要：目的探讨1个鳃裂眼面综合征(BOFS)家系的遗传学病因,并总结文献报道的BOFS患者的产前表型。方法选取2021年12月3日于郑州大学第一附属医院就诊的1个BOFS家系作为研究对象。采集家系相关的临床资料,对胎儿进行系统超声筛查,采用家系全外显子组测序(trio-WES)技术对引产胎儿的组织标本及其父母的外周血样进行检测,对候选变异进行Sanger测序验证及致病性分析。在数据库中检索相关文献,对既往报道的有产前表型的BOFS患者进行总结。本研究通过郑州大学第一附属医院医学伦理委员会的审查(KS-2018-KY-36)。结果系统超声检查提示胎儿存在唇腭裂畸形,胎儿父亲表现为高腭弓、过早白发、隐匿性唇裂、先天性耳前瘘管合并感染、红绿色盲、先天性左肾缺如;胎儿祖父表现为高腭弓、过早白发、招风耳、先天性耳前瘘管、右耳听力下降。Tio-WES检测结果提示胎儿及其父亲均携带TFAP2A基因c.890-1G>A杂合变异,其母亲未检测到相同变异。Sanger测序发现胎儿祖父携带相同变异,符合家系疾病共分离。根据美国医学遗传学与基因组学学会(ACMG)相关指南,该变异被评定为可能致病性(PVS1+PM2_Supporting)。文献检索共获得了36例描述有产前表型的病例,加上上述病例共37例,其中常见的产前表型为生长受限(25/37)、肾脏发育异常(10/37)、唇腭裂畸形(5/37)及羊水过少(5/37)。结论TFAP2A基因c.890-1G>A变异可能是上述家系的遗传学病因。该变异的检出扩展了TFAP2A基因的变异谱。BOFS患者的产前表型主要包括生长受限、肾脏发育异常、唇腭裂畸形及羊水过少等,上述发现对于该病的产前诊断、临床诊疗及家系遗传咨询具有重要的价值。ObjectiveTo explore the genetic etiology of a Chinese pedigree affected with Branchio-oculo-facial syndrome(BOFS)and summarize the prenatal phenotype of BOFS patients.MethodsA pedigree with BOFS which had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University in December 2021 was selected as the study subject.Clinical data of the pedigree was collected.The fetus was subjected to routine prenatal ultrasound scan.Trio-whole exome sequencing(trio-WES)was carried out for the fetus and its parents,and candidate variant was verified by Sanger sequencing.Relevant literature was searched from the database to summarize the prenatal phenotype of BOFS patients.This study was approved by the First Affiliated Hospital of Zhengzhou University(Ethics No.KS-2018-KY-36).ResultsUltrasound exam suggested the fetus had cleft lip and palate.Its father had presented with high palatal arch,prematurely grayed hair,occult cleft lip,congenital preauricular fistula,red-green color blindness and unilateral renal agenesis.Its grandfather also had high palatal arch,prematurely gray hair,protruding ears,congenital preauricular fistula and hearing disorders.Trio-WES revealed that the fetus and its father had both harbored a heterozygous c.890-1G>A variant of the TFAP2A gene.The same variant was not found in its mother.Sanger sequencing confirmed that its grandfather had also harbored the same variant.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was rated as likely pathogenic(PVS1+PM2_Supporting).Combined with 36 similar cases retrieved from the literature,the prenatal phenotypes of BOFS patients had included growth restriction(25/37),renal abnormalities(10/37),cleft lip and palate(5/37)and oligohydramnios(5/37).ConclusionThe c.890-1G>A variant of the TFAP2A gene probably underlay the pathogenesis of BOFS in this pedigree.Discovery of the novel variant has enriched the mutational spectrum of the TFAP2A gene.The common prenatal phenot

关 键 词：鳃裂眼面综合征 唇/腭裂 TFAP2A基因 基因变异 

分 类 号：R714.5[医药卫生—妇产科学]