Frameshift mutation hotspot identified in Smith-Magenis syndrome: case report and review of literature
<p>Abstract</p> <p>Smith-Magenis syndrome (SMS) is a complex syndrome involving intellectual disabilities, sleep disturbance, behavioural problems, and a variety of craniofacial, skeletal, and visceral anomalies. While the majority of SMS cases harbor an ~3.5 Mb common deletion on...
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| Main Authors: | , , , |
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| Format: | Book |
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BMC,
2010-10-01T00:00:00Z.
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| Summary: | <p>Abstract</p> <p>Smith-Magenis syndrome (SMS) is a complex syndrome involving intellectual disabilities, sleep disturbance, behavioural problems, and a variety of craniofacial, skeletal, and visceral anomalies. While the majority of SMS cases harbor an ~3.5 Mb common deletion on 17p11.2 that encompasses the retinoic acid induced-1 (<it>RAI1</it>) gene, some patients carry small intragenic deletions or point mutations in <it>RAI1</it>. We present data on two cases of Smith-Magenis syndrome with mutation of <it>RAI1</it>. Both cases are phenotypically consistent with SMS and <it>RAI1 </it>mutation but also have other anomalies not previously reported in SMS, including spontaneous pneumothoraces. These cases also illustrate variability in the SMS phenotype not previously shown for <it>RAI1 </it>mutation cases, including hearing loss, absence of self-abusive behaviours, and mild global delays. Sequencing of <it>RAI1 </it>revealed mutation of the same heptameric C-tract (CCCCCCC) in exon 3 in both cases (c.3103delC one case and and c.3103insC in the other), resulting in frameshift mutations. Of the seven reported frameshift mutations occurring in poly C-tracts in <it>RAI1</it>, four cases (~57%) occur at this heptameric C-tract. Collectively, these results indicate that this heptameric C-tract is a preferential hotspot for single nucleotide insertion/deletions (SNindels) and therefore, should be considered a primary target for analysis in patients suspected for mutations in <it>RAI1</it>. We expect that as more patients are sequenced for mutations in <it>RAI1</it>, the incidence of frameshift mutations in this hotspot will become more evident.</p> |
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| Item Description: | 10.1186/1471-2350-11-142 1471-2350 |