Kabuki综合征患儿2例的基因变异及临床表型分析  

Analysis of genetic variants and clinical manifestations of two children with Kabuki syndrome

作　　者：沈裕 孙淑妮 解敏 李海波 徐莉敏[1] Shen Yu;Sun Shuni;Xie Min;Li Haibo;Xu Limin(Department of Perinatology,Ningbo Women and Children′s Hospital,Ningbo,Zhejiang 315012,China;Medical School of Ningbo University,Ningbo,Zhejiang 315012,China;Key Laboratory for the Comprehensive Prevention of Birth Defects,Ningbo Women and Children′s Hospital,Ningbo,Zhejiang 315012,China)

机构地区：[1]宁波市妇女儿童医院围产科,宁波315000 [2]宁波大学医学院,宁波315012 [3]宁波市妇女儿童医院出生缺陷综合防治重点实验室,宁波315012

出　　处：《中华医学遗传学杂志》2023年第7期833-837,共5页Chinese Journal of Medical Genetics

基　　金：宁波市科技计划(公益性计划)(202002N3150);宁波市品牌学科(PPXK2018-06);浙江省医药卫生计划(2022503086);宁波市社会发展计划(2021S157);宁波市重点学科(2022-B17)。

摘　　要：目的探讨2例KMT2D基因变异所致Kabuki综合征(KS)的患儿,并总结其临床特征与基因变异的特点。方法以分别于2021年8月19日和11月10日就诊于宁波市妇女儿童医院的2例KS患儿作为研究对象,收集其临床资料,对其进行全外显子组测序(WES),并对候选变异进行Sanger测序家系验证。结果2例患儿均表现为运动、语言发育迟缓、特殊面容、智力障碍等。WES检测发现其分别携带KMT2D基因的c.10205del(p.Leu3402Argfs*3)及c.5104C>T(p.Arg1702*)杂合变异,根据美国医学遗传学和基因组学学会相关指南均评估为致病性变异(PVS1+PM6+PM2_Supporting+PP4)。结论KMT2D基因的c.10205del(p.Leu3402Argfs*3)和c.5104C>T(p.Arg1702*)新发变异可能是2例KS患儿的遗传学病因。上述发现不仅为临床确诊和遗传咨询提供了依据,并且丰富了KMT2D基因的变异谱。Objective To report on two children with Kabuki syndrome due to variants of the KMT2D gene and summarize their clinical and genetic characteristics.Methods Two children who had presented at the Ningbo Women and Children′s Hospital respectively on August 19 and November 10,2021 were selected as the study subjects.Clinical data were collected.Both children were subjected to whole exome sequencing(WES),and candidate variants were validated by Sanger sequencing.Results Both children had featured motor and language developmental delay,facial dysmorphism and mental retardation.Genetic testing revealed that both had harbored de novo heterozygous variants of the KMT2D gene,namely c.10205del(p.Leu3402Argfs*3)and c.5104C>T(p.Arg1702*),both of which were rated as pathogenic variants(PVS1+PM6+PM2_Supporting+PP4)based on the guidelines from the American College of Medical Genetics and Genomics(ACMG).Conclusion The c.10205del(p.Leu3402Argfs*3)and c.5104C>T(p.Arg1702*)variants of the KMT2D gene probably underlay the pathogenesis in these two children.Above finding has not only provided a basis for their diagnosis and genetic counseling,but also enriched the spectrum of KMT2D gene variants.

关 键 词：Kabuki综合征 生长发育迟缓 KMT2D基因 新发变异 

分 类 号：R725.9[医药卫生—儿科]