摘要
目的对5例临床表型严重程度不同的先天性骨骼畸形患儿进行全外显子组测序分析,明确其遗传学病因。总结患者的临床特点并探讨基因型-表型关联分析。方法通过收集5例患儿的临床及影像学资料,采集先证者家系的外周血并提取DNA,患儿行全外显子组测序,通过生物信息学分析并参考ACMG遗传变异分类标准与指南来判断变异位点致病性,Sanger测序验证患儿及父母突变位点。结果5例患儿均携带MYH3基因的错义突变,其中2个错义突变遗传自患儿母亲,分别为:2号患儿c.941T>G(p.Ile314Ser),3号患儿c.3842T>G(p.Leu1281Trp);3个错义突变为新生突变:分别为1号患儿c.853C>G(p.His285Asp),4号患儿c.2621T>C(p.Leu874Pro)和5号患儿c.854A>G(p.His285Arg)。结论发现了MYH3基因的5个变异,不同变异引起的表型严重程度不同且互有重叠,扩展了中国人群MYH3基因变异谱。
Objective To determine the genetic etiology of 5 patients with congenital skeletal malformations of different severity by whole exome sequencing,and to summarize the clinical characteristics and analyze the genotype-phenotype.Methods The clinical and imaging data of 5 patients were collected.The peripheral blood of the proband’s family was collected and DNA was extracted.Whole exome sequencing of patients were performed and variants were classified following the interpretation standards and guidelines of the American College of Medical Genetics and Genomics(ACMG)and the Association for Molecular Pathology.Putative pathogenic variants were verified by Sanger sequencing.Results All five patients carried missense variants in the MYH3 gene.Two missense mutations were maternal,c.941T>G(p.Ile314Ser)in patient 2 and c.3842T>G(p.Leu1281Trp)in patient 3;and three missense mutations were de novo:c.853C>G(p.His285Asp)in patient 1,c.2621T>C(p.Leu874Pro)in patient 4 and c.854A>G(p.His285Arg)in patient 5.Conclusion We found five mutation sites of MYH3.The phenotypes of congenital skeletal diseases caused by different variants of MYH3 have extensive heterogeneity.This result expanded the variation spectrum of MYH3 in the Chinese population.
作者
赵爽
郭若兰
胡旭昀
张学军
郝婵娟
ZHAO Shuang;GUO Ruolan;HU Xuyun;ZHANG Xuejun;HAO Chanjuan(Beijing Key Laboratory for Genetics of Birth Defects,Beijing Pediatric Research Institute,Ministry of Education Key Laboratory of Major Diseases in Children,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing 100045,China;Department of Orthopedics,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing 100045,China;Henan Key Laboratory of Inherited Metabolic Diseases,Pediatric Research Institute of Zhengzhou Children’s Hospital,Children’s Hospital of Zhengzhou University,He’nan Children’s Hospital,Zhengzhou Children’s Hospital,Zhengzhou,He’nan 450053,China)
出处
《中国优生与遗传杂志》
2024年第6期1209-1214,共6页
Chinese Journal of Birth Health & Heredity
基金
国家自然科学基金项目(32270728)
新疆维吾尔自治区重点研发任务专项项目(2023B03018-2)
北京协和医院中央高水平医院临床科研专项(2022-PUMCH-D-004)
作者简介
通讯作者:郝婵娟,hchjhchj@163.com
