A novel compound mutation in GLRA1 cause hyperekplexia in a Chinese boy- a case report and review of the literature

摘要: The pathogenesis of hereditary hyperekplexia is thought to involve abnormalities in the glycinergic neurotransmission system, most mutations reported GLRA1. This gene encodes glycine receptor α1 subunit, which has an extracellular domain (ECD) and a transmembrane (TMD) with 4 α-helices (TM1–TM4). We investigated genetic cause Chinese family one affected member. Whole-exome sequencing 5 candidate genes was performed on proband patient, direct validate confirm detected mutation other members. also review analyse all GLRA1 mutations. had compound heterozygous that comprised 2 novel missense mutations, C.569C > T (p.T190 M) from mother C.1270G > A (p.D424N) father. SIFT, Polyphen-2 MutationTaster analysis identified as disease-causing, but parents no signs hyperekplexia. p.T190 M located ECD, while p.D424N TM4. Our findings contribute growing list associated provide new insights into correlations between phenotype Some recessive can induce combination Mutations TM1, TM1-TM2 loop, TM3, TM3-TM4 loop TM4 are more often part mutation, those TM2 TM2-TM3 likely be dominant