Analysis of genetic variant in a child with Pitt-Hopkins syndrome
朱淑霞 1张园园 2张越华 1鞠翠钰
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作者信息
1. 1滨州医学院附属医院儿童神经科，滨州 256603
2. 2滨州市紧急医学救援指挥中心，滨州 256600
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摘要
目的 探讨1例表现为特殊面容、双手通贯掌、运动及语言发育迟缓、胼胝体发育不良的患儿的遗传学病因。 方法 选取2021年3月16日于滨州医学院附属医院就诊的1例PTHS患儿为研究对象。抽取患儿及其父母的外周血样，提取基因组DNA，进行全外显子组测序及生物信息学分析，并运用Sanger测序技术对候选变异进行验证。 结果 全外显子组测序显示患儿TCF4基因存在c.607delT(p.S203Pfs*31)杂合变异，其父母为野生型。根据美国医学遗传学与基因组学学会(ACMG)相关变异分类标准与指南，c.607delT(p.S203Pfs*31)被评判为致病性变异(PVS1+PM2_Supporting+PM6)。 结论 TCF4基因c.607(exon9)delT杂合变异可能是本例患儿的遗传学病因。 Objective To explore the genetic basis for a child featuring facial dysmorphism, single palmar crease, motor and language delay, and hypoplasia of corpus callosum. Methods A child who had visited the Affiliated Hospital of Binzhou Medical College on March 16, 2021 was selected as the study subject. Peripheral blood samples of the child and his parents were collected, and the genomic DNA was extracted for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results WES revealed that the child has harbored a heterozygous c. 607delT (p.S203Pfs*31) variant in exon 9 of the TCF4 gene, for which both of his parents were of the wild-type. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PM6). Conclusion The heterozygous c. 607delT (p.S203Pfs*31) variant of the TCF4 gene probably underlay the Pitt-Hopkins syndrome in this child. Genetic testing has enabled the definite diagnosis.
Abstract
Objective To explore the genetic basis for a child featuring facial dysmorphism, single palmar crease, motor and language delay, and hypoplasia of corpus callosum. Methods A child who had visited the Affiliated Hospital of Binzhou Medical College on March 16, 2021 was selected as the study subject. Peripheral blood samples of the child and his parents were collected, and the genomic DNA was extracted for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results WES revealed that the child has harbored a heterozygous c. 607delT (p.S203Pfs*31) variant in exon 9 of the TCF4 gene, for which both of his parents were of the wild-type. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PM6). Conclusion The heterozygous c. 607delT (p.S203Pfs*31) variant of the TCF4 gene probably underlay the Pitt-Hopkins syndrome in this child. Genetic testing has enabled the definite diagnosis.
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