Tang Yulin, Li Xiaojing, Wu Wenlin, Shi Zhen, Chen Wenxiong, Tian Yang
Department of Neurology, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510623, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 Jun 10;40(6):696-700. doi: 10.3760/cma.j.cn511374-20220720-00478.
To explore the clinical characteristics and genetic basis of a child with Mental retardation autosomal dominant 51 (MRD51).
A child with MRD51 who was hospitalized at Guangzhou Women and Children's Medical Center on March 4, 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis.
The child, a 5-year-and-3-month-old girl, had manifested autism spectrum disorder (ASD), mental retardation (MR), recurrent febrile convulsions and facial dysmorphism. WES revealed that she has harbored a novel heterozygous variant of c.142G>T (p.Glu48Ter) in the KMT5B gene. Sanger sequencing confirmed that neither of her parents has carried the same variant. The variant has not been recorded in the ClinVar, OMIM and HGMD, ESP, ExAC and 1000 Genomes databases. Analysis with online software including Mutation Taster, GERP++ and CADD indicated it to be pathogenic. Prediction with SWISS-MODEL online software suggested that the variant may have a significant impact on the structure of KMT5B protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic.
The c.142G>T (p.Glu48Ter) variant of the KMT5B gene probably underlay the MRD51 in this child. Above finding has expanded the spectrum of KMT5B gene mutations and provided a reference for clinical diagnosis and genetic counseling for this family.
探讨一名患有常染色体显性遗传智力发育迟缓51型（MRD51）儿童的临床特征及遗传基础。
选取2022年3月4日在广州妇女儿童医疗中心住院的一名患有MRD51的儿童作为研究对象。收集该儿童的临床资料。采集该儿童及其父母的外周血样本，进行全外显子组测序（WES）。通过Sanger测序和生物信息学分析对候选变异进行验证。
该儿童为一名5岁3个月大的女孩，表现为自闭症谱系障碍（ASD）、智力发育迟缓（MR）、反复发热性惊厥和面部畸形。WES显示她在KMT5B基因中存在一个新的杂合变异c.142G>T（p.Glu48Ter）。Sanger测序证实其父母均未携带相同变异。该变异未在ClinVar、OMIM和HGMD、ESP、ExAC及千人基因组数据库中记录。使用Mutation Taster、GERP++和CADD等在线软件分析表明其具有致病性。通过SWISS-MODEL在线软件预测该变异可能对KMT5B蛋白的结构产生重大影响。根据美国医学遗传学与基因组学学会（ACMG）的指南，该变异被预测为致病性变异。
KMT5B基因的c.142G>T（p.Glu48Ter）变异可能是该儿童MRD51的病因。上述发现扩展了KMT5B基因突变谱，为该家庭的临床诊断和遗传咨询提供了参考。
