The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1

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• 作者：Dan Hanson ; Philip G. Murray ; Amit Sud ; Samia A. Temtamy ; Mona Aglan ; Andrea Superti-Furga ; Sue E. Holder ; Jill Urquhart ; Emma Hilton ; Forbes D.C. Manson ; Peter Scambler ; Graeme C.M. Black ; Peter E. Clayton
• 刊名：The American Journal of Human Genetics
• 出版年：2009
• 出版时间：12 June 2009
• 年：2009
• 卷：84
• 期：6
• 页码：801-806
• 全文大小：471 K

文摘

3-M syndrome is an autosomal-recessive primordial growth disorder characterized by significant intrauterine and postnatal growth restriction. Mutations in the CUL7 gene are known to cause 3-M syndrome. In 3-M syndrome patients that do not carry CUL7 mutations, we performed high-density genome-wide SNP mapping to identify a second locus at 2q35-q36.1. Further haplotype analysis revealed a 1.29 Mb interval in which the underlying gene is located and we subsequently discovered seven distinct null mutations from 10 families within the gene OBSL1. OBSL1 is a putative cytoskeletal adaptor protein that localizes to the nuclear envelope. We were also able to demonstrate that loss of OBSL1 leads to downregulation of CUL7, implying a role for OBSL1 in the maintenance of CUL7 protein levels and suggesting that both proteins are involved within the same molecular pathway.