Clinical features and genetic analysis of a case of Wiedemann-Steiner syndrome due to variant ofKMT2A gene
艾奇 1陈云 1陈森 1梁程红 李岭
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作者信息
1. 天津市儿童医院血液科，天津 300134
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摘要
目的 探讨1例Wiedemann-Steiner综合征(WSS)患儿的临床特征及遗传学病因。 方法 选取2015年7月就诊于天津市儿童医院血液科的1例WSS患儿为研究对象。收集患儿的临床资料，采集患儿及其父母的外周血样，提取基因组DNA，对患儿进行全外显子组测序，用Sanger测序对候选变异进行家系验证。 结果 患儿主要表现为全血细胞减少、智力及生长发育落后、特殊面容。全外显子组测序显示其携带KMT2A基因c.7804delA(p.M2602Cfs*39)杂合变异。Sanger测序显示其父母未携带相同的变异。该变异既往未见报道。根据美国医学遗传学和基因组学学会相关指南，判定其为致病性变异(PVS1+PS2+PM2)。 结论 KMT2A基因c.7804delA(p.M2602Cfs*39)杂合变异可能为该WSS征患儿的致病原因。上述发现拓宽了KMT2A基因的变异谱和临床表型谱。 Objective To explore the clinical features and genetic etiology of a child with Wiedemann-Steiner syndrome (WSS). Methods A child with WSS who was admitted to the Hematology Department of Tianjin Children′s Hospital in May 2021 was selected as the subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. The child was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing of the child and his parents. Results The main clinical features of the child have included pancytopenia, growth and mental retardation, and facial dysmorphism. Whole exome sequencing revealed that the child has harbored a heterozygous variant of the KMT2A gene, namely c. 7804delA (p.M2602Cfs*39). Sanger sequencing verified the variant to be de novo in origin. The variant was unreported previously and predicted to be pathogenic based on the guidelines of American College of Medical Genetics and Genomics (PVS1+ PS2+ PM2). Conclusion The heterozygous c. 7804delA (p.M2602Cfs*39) variant of the KMT2A gene probably underlay the WSS in this child. Above finding has enriched the mutational spectrum and clinical phenotypes of the KMT2A gene.
Abstract
Objective To explore the clinical features and genetic etiology of a child with Wiedemann-Steiner syndrome (WSS). Methods A child with WSS who was admitted to the Hematology Department of Tianjin Children′s Hospital in May 2021 was selected as the subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. The child was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing of the child and his parents. Results The main clinical features of the child have included pancytopenia, growth and mental retardation, and facial dysmorphism. Whole exome sequencing revealed that the child has harbored a heterozygous variant of the KMT2A gene, namely c. 7804delA (p.M2602Cfs*39). Sanger sequencing verified the variant to be de novo in origin. The variant was unreported previously and predicted to be pathogenic based on the guidelines of American College of Medical Genetics and Genomics (PVS1+ PS2+ PM2). Conclusion The heterozygous c. 7804delA (p.M2602Cfs*39) variant of the KMT2A gene probably underlay the WSS in this child. Above finding has enriched the mutational spectrum and clinical phenotypes of the KMT2A gene.
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