SMARCA4基因变异致Coffin-Siris综合征4型的临床特点和遗传学分析

Clinical characteristics and genetic analysis of Coffin-Siris syndrome type 4 caused by SMARCA4 gene variants mutation

目的探讨SMARCA4基因变异所致Coffin-Siris综合征4型(CSS4)的临床表型及遗传学特征。方法回顾性分析2023年7月于中山市小榄人民医院诊治的1例以运动发育落后为主诉的CSS4儿童为研究对象。采集该名儿童的临床资料,采用全外显子组测序对该患儿及其生物学父母行遗传学分析,并分析国内外已报道的SMARCA4基因突变所致CSS4病例的临床特点以及遗传学特征。总结已报道SMARCA4所致CSS4的临床特点。结果患儿,男,3岁,以运动发育落后、听力障碍、特殊外貌为临床特点。全外显子组测序结果提示其携带SMARCA4基因c.2576C>T位点移码基因变异,现国内尚未见以该位点变异致使Coffin-Siris综合征4型的文献报道。与6篇国外文献报道的38例SMARCA4基因变异致病患儿,均发生SMARCA4基因变异,存在30种不同的基因变异,其中错义变异最多,主要临床特征表现为智力发育落后者占71.1%、喂养困难者占65.8%、生长发育落后者占57.9%、第五指/足趾发育不良者占55.3%、心血管疾病者占42.1%、头颅影像学异常者占42.1%。结论SMARCA4基因c.2576C>T(p.Thr859Met)是该患儿的病因。本研究丰富了国内SMARCA4相关的CSS4基因变异报道,并为产前诊断分析、临床诊断提供了依据。

Objective To explore the clinical phenotypes and genetic characteristics of Coffin-Siris syndrome type 4(CSS4)caused by SMARCA4 gene mutations.Methods A case of CSS4 children diagnosed and treated at Xiaolan People's Hospital of Zhongshan in July 2023 with main complaints of delayed motor development was retrospectively analyzed.The clinical data of the child were collected,and the genetic analysis was performed on the child and his biological parents using whole-exome sequencing.And the clinical characteristics and genetic characteristics of CSS4 cases caused by SMARCA4 gene mutations that have been reported at home and abroad were analyzed.The clinical features of CSS4 caused by SMACA4 reported in the literature were summarized.Results The patient was a male,3 years old,with clinical characteristics of delayed motor development,hearing impairment,and special appearance.The results of comprehensive medical exome sequencing indicate that he carries the c.2576C>T frameshift gene mutation of the SMARCA4 gene.There are no domestic reports that this site mutation causes Coffin-Siris syndrome type 4.38 cases of children with SMARCA4 gene mutations reported in 6 foreign literatures all had SMARCA4 gene mutations.There were 30 different gene mutations,among which missense mutations were the most common.The main clinical characteristics were that 71.1% of children were mentally retarded.65.8% had feeding difficulties,57.9% had delayed growth and development,55.3% had dysplasia of the fifth finger/toe,42.1% had cardiovascular disease,and 42.1%had abnormal cranial imaging.Conclusion SMARCA4 gene c.2576C>T(p.Thr859Met)is the cause of this child.This study enriches the domestic reports of CSS4 gene variations related to SMARCA4 and provides a basis for prenatal diagnosis analysis and clinical diagnosis.