Article: article from journal or magazin.
The primordial growth disorder 3-M syndrome connects ubiquitination to the cytoskeletal adaptor OBSL1.
American Journal of Human Genetics
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.
Adolescent, Cells, Cultured, Child, Child, Preschool, Cullin Proteins/genetics, Cytoskeletal Proteins/antagonists & inhibitors, Cytoskeletal Proteins/genetics, Cytoskeleton, Female, Growth Disorders/genetics, Humans, Infant, Kidney/cytology, Kidney/metabolism, Male, Mutation/genetics, Oligonucleotide Array Sequence Analysis, Pedigree, Polymorphism, Single Nucleotide/genetics, RNA, Small Interfering/pharmacology, Syndrome, Ubiquitination
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