Journal Article

Missense Mutations in Exon 6 of the Survival Motor Neuron Gene in Patients with Spinal Muscular Atrophy (SMA)

Eric Hahnen, Jutta Schönling, Sabine Rudnik-Schöneborn, Heidrun Raschke, Klaus Zerres and Brunhilde Wirth

in Human Molecular Genetics

Volume 6, issue 5, pages 821-825
Published in print May 1997 | ISSN: 0964-6906
Published online May 1997 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/6.5.821
Missense Mutations in Exon 6 of the Survival Motor Neuron Gene in Patients with Spinal Muscular Atrophy (SMA)

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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, S262I and T274I, 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.

Journal Article.  3735 words.  Illustrated.

Subjects: Genetics and Genomics

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