关键词: 多发先天畸形-肌张力低下-癫痫综合征； 基因； 全外显子测序； ACMG评级

Abstract: 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 MCAHS1 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 CD59 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.343G>C and c.1694G>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 MCAHS1 patients have been reported by literature search. Missense mutation is the most common gene mutation, and most of them have poor prognosis. Conclusion The MCAHS1 gene variant spectrum was expanded due to the gene sequencing of this MCAHS1 child.

Key words: multiple congenital anomalies-hypotonia-seizures syndrome 1; gene; whole exome sequencing; ACMG rating