1 例多发先天畸形- 肌张力低下- 癫痫综合征1 临床及遗传学分析

目的分析多发先天畸形-肌张力低下-癫痫综合征1(MCAHS1)的临床及遗传学特征。方法回顾2018年4月确诊的1例MCAHS1患儿的临床资料;应用全外显子测序及Sanger验证行基因检测;采用流式细胞术分析患儿外周血粒细胞表面糖基磷脂酰肌醇(GPI)锚定蛋白FLAER、CD16、CD24、CD58、CD59表达量。结果男性患儿,4月龄,因阵发性双眼上翻,发育落后就诊;患儿有特殊面容、肌张力低下。全外显子测序发现患儿PIGN基因存在2个杂合变异,c.343G>C和c.1694G>T,分别来自于临床表型正常的母亲和父亲,为复合杂合变异。该变异尚未见报道,经美国医学遗传学与基因组学学会(ACMG)指南评级为疑似致病性变异。该复合杂合变异导致粒细胞表面GPI锚定蛋白的表达量下降。随访发现患儿10月龄出现发热抽搐,15月龄出现癫痫,口服丙戊酸钠后发作控制。经康复治疗患儿仍发育缓慢。文献检索已经报道MCAHS1患者18例,基因变异以错义变异最常见,多数患儿预后不佳。结论该MCAHS1患儿的基因测序扩充了MCAHS 1基因变异谱。

Clinical and genetic analysis of multiple congenital anomalies-hypotonia-seizures syndrome 1:a case report

Objective To explore the clinical and genetic characteristics of multiple congenital anomalies-hypotonia-seizures syndrome 1(MCAHS1).Methods The clinical data of a child diagnosed with MCAHS 1 in April 2018 were reviewed.Gene detection was performed by whole exome sequencing and Sanger verification.Flow cytometry was used to analyze the expression of glycosylphosphatidylinositol(GPI)anchoring proteins FLAER,CD16,CD24,CD58,and CD 59 on the surface of peripheral blood granulocytes.Results A 4-monthold boy was admitted to hospital due to paroxysmal upturning of eyes and underdevelopment.He had special facial features and hypotonia.Two heterozygous mutations(c.343 G>C and c.1694 G>T)were found in the PIGN gene of the child by whole exon sequencing,which came from the mother and father with normal clinical phenotype respectively and were compound heterozygous variants.This variant has not been reported and is classified as suspected pathogenic by the American College of Medical Genetics and Genomics(ACMG)guidelines.The compound heterozygous mutation resulted in the decrease of GPI anchored protein expression on the surface of granulocytes.The followup found that brile convulsions occurred at 10 months of age,epilepsy occurred at 15 months of age and seizures were controlled after oral administration of sodium valproate.After rehabilitation treatment,the child still developed slowly.A total of 18 MCAHS 1 patients have been reported by literature search.Missense mutation is the most common gene mutation,and most of them have poor prognosis.Conclusion The MCAHS 1 gene variant spectrum was expanded due to the gene sequencing of this MCAHS 1 child.