Analysis of genetic variants in a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism without seizures
Analysis of genetic variants in a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism without seizures
仝娇 1王涛 1王雷雷 1闫冬梅 1梁程红
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作者信息
1. 连云港市妇幼保健院，连云港 222000
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摘要
目的 分析1例行为异常和颅面畸形的智力发育障碍但不伴癫痫(IDDBCS)患儿的临床表型和遗传学特征。 方法 选取2021年4月于连云港市妇幼保健院发育行为儿科就诊的1例患儿为研究对象。收集患儿的临床资料，提取患儿及其家系成员的外周血样基因组DNA，用全外显子组测序(WES)筛选患儿可能携带的致病变异位点，用Sanger测序进行家系验证。 结果 患儿为3岁4月龄男性，临床表现为全面性发育迟缓，头部异常。WES检测发现患儿携带PHF21A基因c.1703delA(p.K568Sfs*9)杂合变异。Sanger测序验证患儿携带该变异，其父母该位点为野生型。该变异为低频变异，可能导致编码蛋白质结构和功能变化，根据美国医学遗传学与基因组学学会(ACMG)指南评估为致病性(PVS1+PS2+PM2_Supporting)。 结论 PHF21A基因c.1703delA(p.K568Sfs*9)杂合变异可能是该IDDBCS患儿的遗传学病因。 Objective To explore the clinical phenotype and genetic characteristics of a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial malformations without epilepsy (IDDBCS). Methods A child who had visited the Lianyungang Maternal and Child Health Care Hospital in April 2021 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of his family members. Results The child, a 3-year-and-4-month-old male, had presented with global developmental delay and cranial malformation. Genetic testing revealed that he has harbored a heterozygous c. 1703delA (p.K568Sfs9) variant of the PHF21A gene, for which both of his parents were of the wild type. This low-frequency variant may alter the structure and function of the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+ PS2+ PM2_Supporting). Conclusion The heterozygous c. 1703delA (p.K568Sfs9) variant of the PHF21A gene probably underlay the IDDBCS in this patient.
Abstract
Objective To explore the clinical phenotype and genetic characteristics of a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial malformations without epilepsy (IDDBCS). Methods A child who had visited the Lianyungang Maternal and Child Health Care Hospital in April 2021 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of his family members. Results The child, a 3-year-and-4-month-old male, had presented with global developmental delay and cranial malformation. Genetic testing revealed that he has harbored a heterozygous c. 1703delA (p.K568Sfs9) variant of the PHF21A gene, for which both of his parents were of the wild type. This low-frequency variant may alter the structure and function of the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+ PS2+ PM2_Supporting). Conclusion The heterozygous c. 1703delA (p.K568Sfs9) variant of the PHF21A gene probably underlay the IDDBCS in this patient.
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