[PDF][PDF] The primordial growth disorder 3-M syndrome connects ubiquitination to the cytoskeletal adaptor OBSL1

D Hanson, PG Murray, A Sud, SA Temtamy… - The American Journal of …, 2009 - cell.com
D Hanson, PG Murray, A Sud, SA Temtamy, M Aglan, A Superti-Furga, SE Holder…
The American Journal of Human Genetics, 2009cell.com
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 …
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.
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