Document Detail


The primordial growth disorder 3-M syndrome connects ubiquitination to the cytoskeletal adaptor OBSL1.
MedLine Citation:
PMID:  19481195     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-28
Journal Detail:
Title:  American journal of human genetics     Volume:  84     ISSN:  1537-6605     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-12     Completed Date:  2009-07-02     Revised Date:  2010-09-24    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  801-6     Citation Subset:  IM    
Affiliation:
Endocrine Sciences, Faculty of Medical & Human Sciences, University of Manchester, Manchester, UK.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Cells, Cultured
Child
Child, Preschool
Cullin Proteins / genetics
Cytoskeletal Proteins / antagonists & inhibitors,  genetics*,  metabolism
Cytoskeleton
Female
Growth Disorders / genetics*
Humans
Infant
Kidney / cytology,  metabolism
Male
Mutation / genetics*
Oligonucleotide Array Sequence Analysis
Pedigree
Polymorphism, Single Nucleotide / genetics*
RNA, Small Interfering / pharmacology
Syndrome
Ubiquitination*
Chemical
Reg. No./Substance:
0/CUL7 protein, human; 0/Cullin Proteins; 0/Cytoskeletal Proteins; 0/OBSL1 protein, human; 0/RNA, Small Interfering
Comments/Corrections

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