Identification of mutations in CUL7 in 3-M syndrome.

Details

Serval ID
serval:BIB_37232
Type
Article: article from journal or magazin.
Collection
Publications
Title
Identification of mutations in CUL7 in 3-M syndrome.
Journal
Nature Genetics
Author(s)
Huber C., Dias-Santagata D., Glaser A., O'Sullivan J., Brauner R., Wu K., Xu X., Pearce K., Wang R., Uzielli M.L., Dagoneau N., Chemaitilly W., Superti-Furga A., Dos Santos H., Mégarbané A., Morin G., Gillessen-Kaesbach G., Hennekam R., Van der Burgt I., Black G.C., Clayton P.E., Read A., Le Merrer M., Scambler P.J., Munnich A., Pan Z.Q., Winter R., Cormier-Daire V.
ISSN
1061-4036
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
37
Number
10
Pages
1119-1124
Language
english
Notes
Publication types: Journal Article
Abstract
Intrauterine growth retardation is caused by maternal, fetal or placental factors that result in impaired endovascular trophoblast invasion and reduced placental perfusion. Although various causes of intrauterine growth retardation have been identified, most cases remain unexplained. Studying 29 families with 3-M syndrome (OMIM 273750), an autosomal recessive condition characterized by severe pre- and postnatal growth retardation, we first mapped the underlying gene to chromosome 6p21.1 and then identified 25 distinct mutations in the gene cullin 7 (CUL7). CUL7 assembles an E3 ubiquitin ligase complex containing Skp1, Fbx29 (also called Fbw8) and ROC1 and promotes ubiquitination. Using deletion analysis, we found that CUL7 uses its central region to interact with the Skp1-Fbx29 heterodimer. Functional studies indicated that the 3-M-associated CUL7 nonsense and missense mutations R1445X and H1464P, respectively, render CUL7 deficient in recruiting ROC1. These results suggest that impaired ubiquitination may have a role in the pathogenesis of intrauterine growth retardation in humans.
Keywords
Carrier Proteins/metabolism, Child, Chromosome Mapping, Chromosomes, Human, Pair 6/genetics, Codon, Nonsense, Cullin Proteins/genetics, DNA Mutational Analysis, Female, Fetal Growth Retardation/genetics, Homozygote, Humans, Male, Mutation, Missense, Protein Interaction Mapping, Protein Structure, Tertiary, S-Phase Kinase-Associated Proteins/metabolism, SKP Cullin F-Box Protein Ligases/metabolism, Sequence Deletion, Syndrome
Pubmed
Web of science
Create date
19/11/2007 13:35
Last modification date
03/03/2018 16:03
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