Clinical and genetic analysis of a child with Mental retardation autosomal dominant 51
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目的 探讨1例常染色体显性遗传性智力障碍51型(MRD51)患儿的临床特征与遗传学病因。 方法 选取2022年3月4日于广州市妇女儿童医疗中心就诊的1例MRD51患儿为研究对象。收集患儿临床资料，抽取患儿及其父母外周静脉血样，应用全外显子组测序(WES)对患儿进行基因检测，采用Sanger测序进行家系验证，并对候选变异进行生物信息学分析。 结果 患儿为女性，5岁3个月，具有孤独症谱系障碍(ASD)、智力障碍(MR)、反复热性惊厥、特殊面容等临床表现。WES检测结果提示，患儿KMT5B基因存在c.142G>T (p.Glu48Ter)杂合变异，Sanger测序结果显示患儿父母均未携带该变异，提示为新发变异。生物信息学分析：KMT5B基因c.142G>T (p.Glu48Ter)变异在ClinVar、OMIM、HGMD、ESP、ExAC及1000 Genomes等数据库中，均未见报道；采取Mutation Taster、GERP++及CADD等在线软件对该变异有害性分析结果显示，均提示为致病性变异；采取SWISS-MODEL在线软件预测显示，该变异对KMT5B蛋白结构产生显著影响；根据美国医学遗传学与基因组学学会(ACMG)制定的相关指南，该变异被评级为致病性变异。 结论 KMT5B基因c.142G>T (p.Glu48Ter)变异可能为本研究MRD51患儿的遗传学病因，进一步拓展了KMT5B基因变异谱，为该病患儿临床诊断与遗传咨询提供参考依据。 Objective To explore the clinical characteristics and genetic basis of a child with Mental retardation autosomal dominant 51 (MRD51). Methods 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. Results 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 theKMT5B 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. Conclusion The c. 142G>T (p.Glu48Ter) variant of theKMT5B 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.
Objective To explore the clinical characteristics and genetic basis of a child with Mental retardation autosomal dominant 51 (MRD51). Methods 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. Results 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 theKMT5B 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. Conclusion The c. 142G>T (p.Glu48Ter) variant of theKMT5B 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.
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