title: [SMN1 Gene Point Mutations in Type I-IV Proximal Spinal Muscular Atrophy Patients with a Single Copy of SMN1].
abstract: Type I-IV proximal spinal muscular atrophy (SMA) is one of the most common autosomal-recessive diseas- es, which are characterized in the majority of cases by a severely disabling course. Proximal SMA results from mutations in the telomeric copy of SMN-SMN1 gene. Major SMN1 gene mutation types are deletions in the exons 7 and/or 8, which were revealed to be in the homozygous state in 95% of patients. Deletions in the in- dicated exons of SMN1 gene were revealed in a compound-heterozygous state in combination with intragenic point mutations in the remainder 5% of proximal SMA cases. In the present study, we conducted an analysis of point mutations in eight patients with type I-III proximal SMA phenotype, which had a deletion in 7-8- exons of SMN1 gene in the heterozygous state. We revealed seven different mutations, two of which (c.824G > C (p.Gly275A1a) and c.825-2A > T) are described here for the first time. In addition, mutation c.824G > C (p.Gly275A1a) was observed twice in the examined sample. In seven cases a heterozygous carrier of point mutations was one of the parents of the affected children (in six cases, the father; in one case, the mother). Only one mutation, c.43C > T (p.Gln15X), emerged de novo in a genital cell of the child's father.
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007223:Infant; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D017354:Point Mutation; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*
chemical_list: C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein