目的:分析1例多发性先天性异常-张力减退-癫痫发作综合征1(MCAHS1)患儿的临床表型和遗传病因。
方法:收集2023年3月在青岛大学附属医院就诊的2岁男孩“间歇性肢体抽搐2年”的临床资料。从儿童及其父母收集外周血样本用于全外显子组测序(WES)。根据美国医学遗传学和基因组学学院(ACMG)的指南,通过Sanger测序和生物信息学分析验证了候选变体。
结果:孩子表现出独特的面部特征,肢体畸形,低张力,电机和智力延迟,和癫痫发作。WES透露,他拥有PIGN基因的复合杂合变体,即c.963G>A(p。Q321=)和c.994A>T(p。I332F),遗传自他表型正常的母亲和父亲,分别。根据ACMG指南,c.963g>A被归类为致病变体(PVS1+PM2_支持+PM3),而c.994A>T被归类为不确定意义的变体(PM2_支持+PP3)。
结论:上述发现扩大了与MCAHS1相关的PIGN基因变体的突变谱,这可能有助于描述其基因型-表型相关性。
OBJECTIVE: To analyze the clinical phenotype and genetic etiology of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1).
METHODS: Clinical data of a 2-year-old boy who had presented at the Affiliated Hospital of Qingdao University in March 2023 for \"intermittent limb twitching for 2 years\" was collected. Peripheral blood samples were collected from the child and his parents for whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).
RESULTS: The child had manifested with distinctive facial features, limb deformities, hypotonia, motor and intellectual delays, and epileptic seizures. WES revealed that he has harbored compound heterozygous variants of the PIGN gene, namely c.963G>A (p.Q321=) and c.994A>T (p.I332F), which were inherited from his phenotypically normal mother and father, respectively. Based on the ACMG guidelines, the c.963G>A was classified as a pathogenic variant (PVS1+PM2_Supporting+PM3), whilst the c.994A>T was classified as a variant of uncertain significance (PM2_Supporting+PP3).
CONCLUSIONS: Above discovery has expanded the mutational spectrum of the PIGN gene variants associated with MCAHS1, which may facilitate delineation of its genotype-phenotype correlation.