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Autosomal recessive childhood onset spinal muscular atrophy (SMA) is a leading cause of infant mortality caused by mutations in the survival motor neuron (SMN) gene. The SMN protein is involved in RNA processing and is localised in structures called GEMs in the nucleus. Nothing is yet understood about why mutations in SMN gene result in the selective motor neuron loss observed in patients. The SMN protein domains conserved across several species may indicate functionally significant regions. Exon 3 of SMN contains homology to a tudor domain, where a Type I SMA patient has been reported to harbour a missense mutation. We have generated missense mutants in this region of SMN and have tested their ability to form GEMs when transfected into HeLa cells. Our results show such mutant SMN proteins still localise to GEMs. Furthermore, exon 7 deleted SMN protein appears to exert a dominant negative effect on localisation of endogenous SMN protein. However, exon 3 mutant protein and exon 5 deleted protein exert no such effect.

Original publication




Journal article


Eur J Hum Genet

Publication Date





519 - 525


Amino Acid Sequence, Animals, Cyclic AMP Response Element-Binding Protein, HeLa Cells, Humans, Molecular Sequence Data, Muscular Atrophy, Spinal, Mutagenesis, Site-Directed, Mutation, Nerve Tissue Proteins, RNA-Binding Proteins, SMN Complex Proteins, Sequence Homology, Amino Acid