The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1
The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1
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DOI：
10.1016/j.ajhg.2009.04.021
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发表时间：
2009-06-12
影响因子：
9.8
通讯作者：
Clayton, Peter E.
中科院分区：
文献类型：
--
作者：
Hanson, Dan;Murray, Philip G.;Clayton, Peter E.
3-M 综合征是一种常染色体隐性原始生长障碍，其特征是显着的宫内和产后生长受限。已知 CUL7 基因突变会导致 3-M 综合征。在不携带 CUL7 突变的 3-M 综合征患者中，我们进行了高密度全基因组 SNP 作图，以确定 2q35-c36.1 处的第二个基因座。进一步的单倍型分析揭示了潜在基因所在的 1.29 Mb 间隔，随后我们在基因 OBSL1 内发现了来自 10 个家族的 7 个不同的无效突变。 OBSL1 是一种假定的细胞骨架衔接蛋白，定位于核膜。我们还能够证明 OBSL1 的缺失会导致 CUL7 的下调，这意味着 OBSL1 在维持 CUL7 蛋白水平中发挥作用，并表明这两种蛋白参与相同的分子途径。
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-c36.1. 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.