Human Molecular Genetics, Vol 6, 821-825, Copyright © 1997 by Oxford University Press
E Hahnen, J Schonling, S Rudnik-Schoneborn, H Raschke, K Zerres and B Wirth
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.
ARTICLES
Missense mutations in exon 6 of the survival motor neuron gene in patients with spinal muscular atrophy (SMA)
Institute of Human Genetics, Bonn, Germany.
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