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MYH3基因突变的先天性骨骼畸形患儿的遗传学研究

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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.
Genetic characteristics of patients with MYH3-associated congenital skeletal malformations
Objective To determine the genetic etiology of 5 patients with congenital skeletal malformations of dif-ferent 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 col-lected 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 Associa-tion for Molecular Pathology.Putative pathogenic variants were verified by Sanger sequencing.Results All five patients car-ried 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.

MYH3 genecongenital skeletal malformationsgenotype-phenotype correlation

赵爽、郭若兰、胡旭昀、张学军、郝婵娟

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国家儿童医学中心/首都医科大学附属北京儿童医院/北京市儿科研究所/出生缺陷遗传学研究北京市重点实验室/儿科重大疾病研究教育部重点实验室,北京 100045

郑州大学附属儿童医院/河南省儿童医院/郑州儿童医院儿科研究所/河南省儿童遗传代谢疾病重点实验室,河南郑州 450053

国家儿童医学中心/首都医科大学附属北京儿童医院骨科,北京 100045

MYH3基因 先天性骨骼畸形 基因型-表型关联性

国家自然科学基金项目新疆维吾尔自治区重点研发任务专项项目北京协和医院中央高水平医院临床科研专项

322707282023B03018-22022-PUMCH-D-004

2024

中国优生与遗传杂志
中国优生科学协会

中国优生与遗传杂志

CSTPCD
影响因子:0.527
ISSN:1006-9534
年,卷(期):2024.32(6)