title: Hybrid survival motor neuron genes in Japanese patients with spinal muscular atrophy.
abstract: Spinal muscular atrophy (SMA) is a frequently occurring autosomal recessive disease, characterized by the degeneration of spinal cord anterior horn cells, leading to muscular atrophy. Most SMA patients carry homozygous deletions of the telomeric survival motor neuron gene (SMN) exons 7 and 8. In the study presented here, we examined 20 Japanese SMA patients and found that 4 of these patients were lacking in telomeric SMN exon 7, but retained exon 8. In these 4 patients, who exhibited all grades of disease severity, direct sequencing analysis demonstrated the presence of a hybrid SMN gene in which centromeric SMN exon 7 was adjacent to telomeric SMN exon 8. In an SMA family, a combination of polymerase chain reaction and enzyme-digestion analysis and haplotype analysis with the polymorphic multicopy marker Agl-CA indicated that the patient inherited the hybrid gene from her father. In conclusion, hybrid SMN genes can be present in all grades of disease severity and inherited from generation to generation in an SMA family.
authors.affiliation: Department of Public Health, Kobe University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nishio
authors.forename: H
authors.initials: H
authors.lastname: Horikawa
authors.forename: H
authors.initials: H
authors.lastname: Yakura
authors.forename: K
authors.initials: K
authors.lastname: Sugie
authors.forename: T
authors.initials: T
authors.lastname: Nakamuro
authors.forename: K
authors.initials: K
authors.lastname: Koterazawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: M J
authors.initials: MJ
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: Y
authors.initials: Y
authors.lastname: Takeshima
authors.forename: M
authors.initials: M
authors.lastname: Matsuo
authors.forename: K
authors.initials: K
authors.lastname: Sumino
mesh_terms: D000328:Adult; D001483:Base Sequence; D002675:Child, Preschool; D017362:Cyclic AMP Response Element-Binding Protein; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005785:Gene Conversion / Q000235:genetics*; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000145:classification / Q000208:ethnology / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009679:Nuclear Family; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins