KMT2D基因新发变异所致歌舞伎综合征4例患儿的临床及遗传学特征

Clinical and genetic characteristics of four children with Kabuki syndrome due to de novo variants of KMT2D gene

目的探讨4例KMT2D基因变异所致的歌舞伎综合征(KS)患儿的临床及遗传学特点。方法选取2020年1月至2022年12月就诊于山西省儿童医院的4例KS患儿作为研究对象。对4例患儿及其家系成员进行全外显子组测序,并对候选变异进行Sanger测序家系验证和致病性分析。结果4例患儿的KS表型评分分别为7分、8分、6分和6分,患儿2还伴有罕见的孤肾畸形。基因检测结果显示4例患儿分别携带KMT2D基因c.16472_16473del、c.858dup、c.11899C>T和c.12844C>T新发变异,根据美国医学遗传学与基因组学学会(ACMG)相关指南,上述变异均被判定为致病性。结论对表现为特殊面容、智力低下、发育迟缓、心脏发育异常、泌尿系统异常等表型的患儿,需考虑KS并尽早通过基因检测实现早期诊断和干预。

Objective To explore the clinical and genetic characteristics of four children with Kabuki syndrome(KS)due to variants of KMT2D gene.Methods Four children with KS diagnosed at the Children′s Hospital of Shanxi Province between January 2020 and December 2022 were selected as the study subjects.Whole exome sequencing was carried out for the children and their family members.Candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results The KS phenotype scores for the four children were 7,8,6,and 6,respectively.Child 2 also presented with a rare solitary kidney malformation.Genetic testing revealed that all children had harbored novel de novo variants of the KMT2D gene,including c.16472_16473del,c.858dup,c.11899C>T,and c.12844C>T,respectively.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),all of the variants were classified as pathogenic.Conclusion For children showing phenotypes such as distinctive facial features,intellectual disability,developmental delay,cardiac abnormalities,and urinary system anomalies,KS should be considered.Early diagnosis and intervention can be achieved through genetic testing,especially in the presence of KMT2D gene mutations.