Two novel missense mutations in hairy-and-enhancer-of-split-7 in a family with spondylocostal dysostosis
Data(s) |
01/06/2010
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Resumo |
Spondylocostal dysostosis (SCD) is an inherited disorder with abnormal vertebral segmentation that results in extensive hemivertebrae, truncal shortening and abnormally aligned ribs. It arises during embryonic development by a disruption of formation of somites (the precursor tissue of the vertebrae, ribs and associated tendons and muscles). Four genes causing a subset of autosomal recessive forms of this disease have been identified: <i>DLL3</i> (SCDO1: MIM 277300), <i>MESP2</i> (SCDO2: MIM 608681), <i>LFNG</i> (SCDO3: MIM609813) and <i>HES7</i> (SCDO4). These genes are all essential components of the Notch signalling pathway, which has multiple roles in development and disease. Previously, only a single SCD-causative missense mutation was described in <i>HES7</i>. In this study, we have identified two new missense mutations in the <i>HES7</i> gene in a single family, with only individuals carrying both mutant alleles being affected by SCD. In vitro functional analysis revealed that one of the mutant <i>HES7</i> proteins was unable to repress gene expression by DNA binding or protein heterodimerization.<br /> |
Identificador | |
Idioma(s) |
eng |
Publicador |
Nature Publishing Group |
Relação |
http://dro.deakin.edu.au/eserv/DU:30038986/wouters-twonovelmissense-2010.pdf http://dx.doi.org/10.1038/ejhg.2009.241 |
Direitos |
2010, Nature Publishing Group |
Palavras-Chave | #HES7 #notch signalling #somitogenesis #abnormal vertebral segmentation |
Tipo |
Journal Article |