Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
OBSL1 mutations in 3-M syndrome are associated with a modulation of IGFBP2 and IGFBP5 expression levels
Human Mutation, Volume 31, No. 1, Year 2010
Notification
URL copied to clipboard!
Description
3-M syndrome is an autosomal recessive disorder characterized by severe pre- and postnatal growth retardation and minor skeletal changes. We have previously identified CUL7 as a disease-causing gene but we have also provided evidence of genetic heterogeneity in the 3-M syndrome. By homozygosity mapping in two inbred families, we found a second disease locus on chromosome 2q35-36.1 in a 5.2-Mb interval that encompasses 60 genes. To select candidate genes, we performed microarray analysis of cultured skin fibroblast RNA from one patient, looking for genes with altered expression; we found decreased expression of IGFBP2 and increased expression of IGFBP5. However, direct sequencing of these two genes failed to detect any anomaly. We then considered other candidate genes by their function/location and found nine distinct mutations in the OBSL1 gene in 13 families including eight nonsense and one missense mutations. To further understand the links between OBSL1, CUL7, and insulin-like growth factor binding proteins (IGFBPs), we performed real-time quantitative PCR (RT-PCR) analysis for OBSL1, CUL7, IGFBP2, and IGFBP5, using cultured fibroblast RNAs from two patients with distinct OBSL1 mutations (p.F697G; p.H814RfsX15). We found normal CUL7 mRNA levels but abnormal IGFBP2 and IGFBP5 mRNA levels in the two patients, suggesting that OBSL1 modulates the expression of IGFBP proteins. © 2009 Wiley-Liss, Inc.
Authors & Co-Authors
Huber, Céline
France, Paris
Université Paris Cité
Fradin, Mélanie
France, Paris
Université Paris Cité
Édouard, Thomas
France, Toulouse
Hôpital Purpan
Le Merrer, Martine F.
France, Paris
Université Paris Cité
Alanay, Yasemin
Turkey, Ankara
Ihsan Dogramaci Children's Hospital
Da Silva, Daniela Bezerra
Canada, Montreal
Chu Sainte-justine - le Centre Hospitalier Universitaire Mère-enfant
David, Albert
France, Nantes
Nantes Hospital
Hamamy, Hanan Ali
Jordan, Amman
National Center for Diabetes, Endocrinology and Genetics Jordan
van Hest, Liselotte P.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Lund, Allan Meldgaard Y.
Denmark, Copenhagen
Copenhagen University Hospital
Michaud, Jacques L.
Canada, Montreal
Chu Sainte-justine - le Centre Hospitalier Universitaire Mère-enfant
Oley, Christine A.
United Kingdom, Birmingham
Birmingham Women's Hospital
Patel, Chirag
United Kingdom, Birmingham
Birmingham Women's Hospital
Rajab, Anna A.
Oman, Muscat
Royal Hospital
Skidmore, David L.
Canada, Halifax
Dalhousie University
Stewart, Helen
United Kingdom, Oxford
Churchill Hospital
Tauber, Maité
France, Toulouse
Hôpital Purpan
Münnich, Arnold
France, Paris
Université Paris Cité
Cormier-Dairé, Valeŕie
France, Paris
Université Paris Cité
Statistics
Citations: 36
Authors: 19
Affiliations: 12
Identifiers
Doi:
10.1002/humu.21150
ISSN:
10597794
Research Areas
Genetics And Genomics
Health System And Policy
Maternal And Child Health
Study Approach
Quantitative