Sparrow, Duncan B and McInerney-Leo, Aideen and Gucev, Zoran S and Gardiner, Brooke and Marshall, Mhairi and Leo, Paul J and Chapman, Deborah L and Tasic, Velibor and Shishko, Abduhadi and Brown, Matthew A and Duncan, Emma L and Dunwoodie, Sally L (2013) Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6. Human Molecular Genetics, 22 (8). pp.1625-31. ISSN 1460-2083 (OA)
Full text not available from this repository.Abstract
In humans, congenital spinal defects occur with an incidence of 0.5-1 per 1000 live births. One of the most severe syndromes with such defects is spondylocostal dysostosis (SCD). Over the past decade, the genetic basis of several forms of autosomal recessive SCD cases has been solved with the identification of four causative genes (DLL3, MESP2, LFNG and HES7). Autosomal dominant forms of SCD have also been reported, but to date no genetic etiology has been described for these. Here, we have used exome capture and next-generation sequencing to identify a stoploss mutation in TBX6 that segregates with disease in two generations of one family. We show that this mutation has a deleterious effect on the transcriptional activation activity of the TBX6 protein, likely due to haploinsufficiency. In mouse, Tbx6 is essential for the patterning of the vertebral precursor tissues, somites; thus, mutation of TBX6 is likely to be causative of SCD in this family. This is the first identification of the genetic cause of an autosomal dominant form of SCD, and also demonstrates the potential of exome sequencing to identify genetic causes of dominant diseases even in small families with few affected individuals.
(NHMRC grants 635500 and 1044543).
| Item Type: | Article |
|---|---|
| Additional Information: | Article available for free from publisher's website. |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 22 Dec 2015 04:13 |
| Last Modified: | 15 Feb 2017 22:25 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/68 |
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