一例ATP6V0A2基因变异所致常染色体隐性皮肤松弛症患儿的临床特征及遗传学分析  

Analysis of clinical features and genetic variants in a child with autosomal recessive cutis laxa due to variants of ATP6V0A2 gene

作　　者：朱融和[1] 王楸[1] 凌雅[1] Zhu Ronghe;Wang Qiu;Ling Ya(Department of Pediatrics,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang 325000,China)

机构地区：[1]温州医科大学附属第一医院儿科,浙江325015

出　　处：《中华医学遗传学杂志》2022年第10期1135-1139,共5页Chinese Journal of Medical Genetics

基　　金：温州市基础性科研项目(Y20210274)。

摘　　要：目的探讨一例ATP6V0A2基因相关常染色体隐性皮肤松弛症(autosomal recessive cutis laxa,ARCL)患儿的临床表现及遗传学特点。方法收集1例ATP6V0A2基因相关ARCL患儿的临床资料,对患儿进行全外显子组测序分析(trio-whole exome sequencing,trio-WES),Sanger测序对可能的变异位点进行验证,并复习文献总结该类疾病的临床表现和遗传学特征。结果患儿5岁2月龄,身高109.5 cm(40%),体重14.2 kg(<3%),眼裂下斜、眼距宽、宽鼻梁、前额突、长人中,腹部、双侧腹股沟皮肤松弛、皱纹明显,双侧隐睾,既往有"脐疝"病史,ATP6V0A2基因存在复合杂合变异,包含1个移码变异c.1421_1424delAGTC(p.Val476Thrfs*71)和1个剪接位点变异c.2293+1G>A,2个变异位点文献均未见报道。本研究对既往文献报道的75例ATP6V0A2基因相关ARCL患者的临床表型进行分析,结果显示皮肤松弛(100%,75/75)、特殊面容(78.7%,59/75)和前囟大或闭合延迟(65.3%,49/75)是最常见临床特征,眼裂下斜(57.3%,43/75)、宽鼻梁(40.0%,30/75)和长脸(34.7%,26/75)是最常见的面部特征。结论当患者出现皮肤松弛,合并特殊面容、前囟大或闭合延迟、生长发育迟缓、智力发育迟缓和癫痫等应考虑ATP6V0A2基因相关ARCL。全外显子组测序是一种快速鉴定致病变异的精确方法,有助于早期确诊。Objective To explore the clinical characteristics and genetic basis for a child featuring autosomal recessive cutis laxa(ARCL).Methods Clinical data of the patient was collected.Trio-whole exome sequencing(trio-WES)was carried out for the proband,his sister and parents.Candidate variant was verified by Sanger sequencing.Results The 5 years and 2 month old child,was 109.5 cm tall(40%centile)and 14.2 kg in weight(<3%centile).Physical examination discovered facial dysmorphisms including downslanting palpebral fissure,hypertelorism,broad nasal bridge,prominent forehead,long philtrum,obvious loose and wrinkled of abdominal and groin skin.He also had previous history of cryptorchidism and umbilical hernia.Trio-WES revealed that the child harbored compound heterozygous variants c.1421_1424delAGTC(p.Val476Thrfs*71)and c.2293+1G>A of the ATP6V0A2 gene,both of which were unreported previously.In addition to our patient,75 cases of ATP6V0A2 gene-related ARCL have so far been diagnosed,with main features including cutis laxa[100%(75/75)],facial dysmorphism[78.7%(59/75)]and delayed closure/large anterior fontanelle[65.3%(49/75)].Typical facial features have included downslanting palpebral fissures[57.3%(43/75)],broad nasal bridge[40.0%(30/75)]and long face[34.7%(26/75)].Conclusion Patients presenting with generalized skin wrinkling,facial dysmorphism,delayed closure/large anterior fontanelle,mental retardation,global developmental disabilities and seizures should be considered for ATP6V0A2 gene-related ARCL.Exome sequencing may facilitate the identification of genetic etiology,to confirm the diagnosis.

关 键 词：ATP6V0A2基因 常染色体隐性皮肤松弛症 特殊面容 

分 类 号：R725.9[医药卫生—儿科]