title: Missense mutations in exon 6 of the survival motor neuron gene in patients with spinal muscular atrophy (SMA).
abstract: Spinal muscular atrophy (SMA) is a frequent autosomal recessive neurodegenerative disorder leading to weakness and atrophy of voluntary muscles. The survival motor neuron gene (SMN) is a strong candidate for SMA and present in two highly homologous copies (telSMN and cenSMN) within the SMA region (5q11.2-q13.3). More than 90% of SMA patients show homozygous deletions of at least exon 7 of telSMN, whereas absence of cenSMN seems to have no clinical consequences. In 23 non-deleted SMA patients, we searched for intragenic mutations of the SMN genes in exons 1-7 and the promotor region by single strand conformation analysis. We identified two different missense mutations, S2621 and T2741, in exon 6 of telSMN in three independent SMA families, providing further evidence for the telSMN gene as a SMA determining gene. Both mutations, as well as two previously described mutations (Y272C and G279V) are located within a highly conserved interval from codon 258 to codon 279 which seems to be an important functional domain of the telSMN protein. Recently, this region has been shown to contain a tyrosine/glycine-rich motif, which is also present in various RNA binding proteins, suggesting a potential role of SMN in RNA metabolism. Missense mutations might be useful for in vivo and transgenic experiments and further investigations on understanding the function of the telSMN protein.
authors.affiliation: Institute of Human Genetics, Bonn, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Hahnen
authors.forename: J
authors.initials: J
authors.lastname: Schönling
authors.forename: S
authors.initials: S
authors.lastname: Rudnik-Schöneborn
authors.forename: H
authors.initials: H
authors.lastname: Raschke
authors.forename: K
authors.initials: K
authors.lastname: Zerres
authors.forename: B
authors.initials: B
authors.lastname: Wirth
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D002648:Child; D002675:Child, Preschool; D017362:Cyclic AMP Response Element-Binding Protein; D005091:Exons; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins