SOX5基因新发变异致Lamb-Shaffer综合征1例患儿的临床及遗传学分析  

Clinical and genetic analysis of a child with Lamb-Shaffer syndrome due to a de novo variant of SOX5 gene

作　　者：张利明 石立业 李林飞 杨建伟[1] 孙红启 杨俊梅[1] 陈永兴 Zhang Liming;Shi Liye;Li Linfei;Yang Jianwei;Sun Hongqi;Yang Junmei;Chen Yongxing(Department of Clinical Laboratory,Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou Key Laboratory of Children′s Infection and Immunity,Zhengzhou,Henan 450018,China;Department of Rehabilitation Medicine,Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou,Henan 450018,China;Pediatric Medical Institute,Children′s Hospital Affiliated to Zhengzhou University,Henan Provincial Key Laboratory for Genetic and Metabolic Disease in Children,Zhengzhou,Henan 450018,China;Department of Endocrine Genetics and Metabolism,Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou,Henan 450018,China)

机构地区：[1]郑州大学附属儿童医院检验科,郑州市儿童感染与免疫重点实验室,郑州450018 [2]郑州大学附属儿童医院康复医学科,郑州450018 [3]郑州大学附属儿童医院儿研所,河南省儿童遗传代谢性疾病重点实验室,郑州450018 [4]郑州大学附属儿童医院内分泌遗传代谢科,郑州450018

出　　处：《中华医学遗传学杂志》2025年第1期89-93,共5页Chinese Journal of Medical Genetics

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20240560)。

摘　　要：目的探讨1例SOX5基因变异所致Lamb-Shaffer综合征患儿的临床特点和基因变异。方法选取郑州大学附属儿童医院2022年7月诊治的1例患儿为研究对象,回顾性分析其临床特征。收集患儿的临床资料,对患儿及其父母的外周血样本进行全外显子组测序(WES),对候选变异进行Sanger测序验证与生物信息学分析。本研究通过了郑州大学附属儿童医院医学伦理委员会的审查(批准号:2024-K-100)。结果患儿为1岁7个月男性,精神、言语和语言、智力及运动等全面发育迟缓,伴有轻度面部畸形及眼征。全外显子组测序及Sanger测序结果显示其SOX5基因存在c.1828_1829insGACT(p.Y610fs*1)杂合移码变异,其父母均未携带此变异,且既往未见报道。根据美国医学遗传学与基因组学学会(ACMG)相关指南评判为致病变异(PVS1+PS2+PM2_supporting)。结论SOX5基因新发变异考虑为该Lamb-Shaffer综合征患儿的遗传学病因。对存在精神、语言、智力、运动等全面发育落后的患儿,应警惕Lamb-Shaffer综合征的可能,通过基因检测尽早明确诊断。本研究的发现亦扩展了SOX5基因的变异谱。ObjectiveTo explore the clinical features of a child with Lamb-Shaffer syndrome(LAMSHF)due to a variant of SOX5 gene.MethodsA child who was admitted to Children′s Hospital Affiliated to Zhengzhou University in July 2022 was selected as the study subject.Clinical data of the child was collected.Whole exome sequencing(WES)was carried out on peripheral blood samples from the child and his parents,and candidate variant was verified by Sanger sequencing and bioinformatic analysis.The study has been approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University(Ethics No.2024-K-100).ResultsThe child,an one-year-and-seven-month-old male,has manifested delayed development in speech and language,intelligence and movement,in addition with mild facial deformities and eye signs.Whole exome sequencing revealed that he has harbored a heterozygous c.1828_1829insGACT(p.Y610fs*1)frameshifting variant of the SOX5 gene.Sanger sequencing confirmed the variant to be de novo in origin.The variant was also unreported previously.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was rated as pathogenic(PVS1+PS2+PM2_supporting).ConclusionThe c.1828_1829insGACT(p.Y610fs*1)variant of the SOX5 gene probably underlay the pathogenesis of LAMSHF in this child.For children with delayed mental,language,intellectual,and motor development,genetic testing should be conducted to facilitate early diagnosis.Above finding has enriched the mutational spectrum of the SOX5 gene.

关 键 词：Lamb-Shaffer综合征 SOX5基因 全外显子组测序 发育迟缓 

分 类 号：R725.9[医药卫生—儿科]