KMT2D基因变异相关歌舞伎综合征1例的遗传学分析  

Analysis of a case of Kabuki syndrome due to a novel variant of KMT2D gene

作　　者：黄娟 李秋雨 吉炜 郭晓峰 林少勇[1,4] 胡晓虹 Huang Juan;Li Qiuyu;Ji Wei;Guo Xiaofeng;Lin Shaoyong;Hu Xiaohong(Department of Cardiology,Fujian Children′s Hospital,Fuzhou,Fujian 350011,China;Department of Cardiology,Beijing Anzhen Hospital,Capital Medical University/Beijing Institute of Cardiopulmonary and Vascular Diease,Beijing 100029,China;Department of Cardiology,Shanghai Children′s Medical Center,Shanghai 200127,China;Department of Pediatrics,Fujian Maternal and Child Health Care Hospital,Fuzhou,Fujian 350001,China;Department of Cardiology,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200082,China)

机构地区：[1]福建省儿童医院心内科,福州350011 [2]首都医科大学附属北京安贞医院心内科/北京市心肺血管病研究所,北京100029 [3]上海交通大学附属上海儿童医学中心心内科,上海200127 [4]福建省妇幼保健院儿科,福州350001 [5]上海交通大学医学院附属新华医院心内科,上海200082

出　　处：《中华医学遗传学杂志》2024年第3期356-362,共7页Chinese Journal of Medical Genetics

摘　　要：目的探讨1例KMT2D基因变异的歌舞伎综合征(KS)患儿的遗传学特征。方法选取2022年7月25日于福建省儿童医院就诊的1例KS患儿作为研究对象进行回顾性研究。对患儿及其父母进行全外显子组测序,并应用Sanger测序对候选变异进行验证,通过相关数据库及软件对其进行致病性分析。结果患儿为4月龄女性,临床特征包括特殊面容、生长发育迟缓、心脏畸形、马蹄肾、甲状腺功能减退以及反复吸入性肺炎。全外显子组测序显示该患儿存在KMT2D基因c.6285dup(p.Lys2096Ter)杂合变异,Sanger测序验证其父母均未携带该变异,提示其为新发变异。该变异位点具有高度保守性,蛋白功能分析提示蛋白截短,酶促活性区域丢失。根据美国医学遗传学与基因组学学会(ACMG)相关指南,该变异被评定为致病性变异(PVS1+PS2+PM2_Supporting)。结论KMT2D基因c.6285dup变异可考虑为患儿患KS的致病原因。Objective To report on a case of Kabuki syndrome(KS)due to a novel variant of KMT2D gene.Methods A child diagnosed with KS at the Fujian Children′s Hospital on July 25,2022 was selected as the study subject.Whole exome sequencing was carried out for the child and her parents.Candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results The child,a 4-month-old female,had presented with distinctive facial features,growth retardation,cardiac malformations,horseshoe kidney,hypothyroidism,and recurrent aspiration pneumonia.Whole exome sequencing revealed that she has harbored a heterozygous c.6285dup(p.Lys2096Ter)variant of the KMT2D gene.Sanger sequencing confirmed that neither of her parents had carried the same variant.The variant was previously unreported,and may result in a truncated protein and loss of an enzymatic activity region.The corresponding site of the variant is highly conserved.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was classified as pathogenic(PVS1+PS2+PM2_Supporting).Conclusion The c.6285 dup variant of the KMT2D gene probably underlay the KS in this child.

关 键 词：发育障碍 歌舞伎综合征 KMT2D基因 基因变异 

分 类 号：R725.9[医药卫生—儿科]