Subtle mutations in the <it>SMN1</it> gene in Chinese patients with SMA: p.Arg288Met mutation causing <it>SMN1</it> transcript exclusion of exon7
<p>Abstract</p> <p>Background</p> <p>Proximal spinal muscular atrophy (SMA) is a common neuromuscular disorder resulting in death during childhood. Around 81 ~ 95% of SMA cases are a result of homozygous deletions of survival motor neuron gene 1 (<it>SMN1</it&g...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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BMC,
2012-09-01T00:00:00Z.
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| Summary: | <p>Abstract</p> <p>Background</p> <p>Proximal spinal muscular atrophy (SMA) is a common neuromuscular disorder resulting in death during childhood. Around 81 ~ 95% of SMA cases are a result of homozygous deletions of survival motor neuron gene 1 (<it>SMN1</it>) gene or gene conversions from <it>SMN1</it> to <it>SMN2</it>. Less than 5% of cases showed rare subtle mutations in <it>SMN1</it>. Our aim was to identify subtle mutations in Chinese SMA patients carrying a single <it>SMN1</it> copy.</p> <p>Methods</p> <p>We examined 14 patients from 13 unrelated families. Multiplex ligation-dependent probe amplification analysis was carried out to determine the copy numbers of <it>SMN1</it> and <it>SMN2</it>. Reverse transcription polymerase chain reaction (RT-PCR) and clone sequencing were used to detect subtle mutations in <it>SMN1</it>. <it>SMN</it> transcript levels were determined using quantitative RT-PCR.</p> <p>Results</p> <p>Six subtle mutations (p.Ser8LysfsX23, p.Glu134Lys, p.Leu228X, p.Ser230Leu, p.Tyr277Cys, and p.Arg288Met) were identified in 12 patients. The p.Tyr277Cys mutation has not been reported previously. The p.Ser8LysfsX23, p.Leu228X, and p.Tyr277Cys mutations have only been reported in Chinese SMA patients and the first two mutations seem to be the common ones. Levels of full length <it>SMN1</it> (fl-<it>SMN1)</it> transcripts were very low in patients carrying p.Ser8LysfsX23, p.Leu228X or p.Arg288Met compared with healthy carriers. In patients carrying p.Glu134Lys or p.Ser230Leu, levels of fl-<it>SMN1</it> transcripts were reduced but not significant. The <it>SMN1</it> transcript almost skipped exon 7 entirely in patients with the p.Arg288Met mutation.</p> <p>Conclusions</p> <p>Our study reveals a distinct spectrum of subtle mutations in <it>SMN1</it> of Chinese SMA patients from that of other ethnicities. The p.Arg288Met missense mutation possibly influences the correct splicing of exon 7 in <it>SMN1</it>. Mutation analysis of the <it>SMN1</it> gene in Chinese patients may contribute to the identification of potential ethnic differences and enrich the <it>SMN1</it> subtle mutation database.</p> |
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| Item Description: | 10.1186/1471-2350-13-86 1471-2350 |