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
WNT1 mutations in families affected by moderately severe and progressive recessive osteogenesis imperfecta
American Journal of Human Genetics, Volume 92, No. 4, Year 2013
Notification
URL copied to clipboard!
Description
Osteogenesis imperfecta (OI) is a heritable disorder that ranges in severity from death in the perinatal period to an increased lifetime risk of fracture. Mutations in COL1A1 and COL1A2, which encode the chains of type I procollagen, result in dominant forms of OI, and mutations in several other genes result in recessive forms of OI. Here, we describe four recessive-OI-affected families in which we identified causative mutations in wingless-type MMTV integration site family 1 (WNT1). In family 1, we identified a homozygous missense mutation by exome sequencing. In family 2, we identified a homozygous nonsense mutation predicted to produce truncated WNT1. In family 3, we found a nonsense mutation and a single-nucleotide duplication on different alleles, and in family 4, we found a homozygous 14 bp deletion. The mutations in families 3 and 4 are predicted to result in nonsense-mediated mRNA decay and the absence of WNT1. WNT1 is a secreted signaling protein that binds the frizzled receptor (FZD) and the coreceptor low-density lipoprotein-receptor- related protein 5 (LRP5). Biallelic loss-of-function mutations in LRP5 result in recessive osteoporosis-pseudoglioma syndrome with low bone mass, whereas heterozygous gain-of-function mutations result in van Buchem disease with elevated bone density. Biallelic loss-of-function mutations in WNT1 result in a recessive clinical picture that includes bone fragility with a moderately severe and progressive presentation that is not easily distinguished from dominant OI type III. © 2013 The American Society of Human Genetics.
Authors & Co-Authors
Pyott, Shawna M.
United States, Seattle
University of Washington
Tran, Thao T.
United States, Seattle
University of Washington
Leistritz, Dru F.
United States, Seattle
University of Washington
Pepin, Melanie G.
United States, Seattle
University of Washington
Mendelsohn, Nancy J.
United States, Minneapolis
Children's Hospitals and Clinics of Minnesota
United States, Minneapolis
University of Minnesota Twin Cities
Temme, Renee T.
United States, Minneapolis
Children's Hospitals and Clinics of Minnesota
Fernandez, Bridget A.
Canada, St John's
Memorial University of Newfoundland
Elsayed, Solaf M.
Egypt, Cairo
Faculty of Medicine - Ain Shams University
Elsobky, Ezzat S.
Egypt, Cairo
Faculty of Medicine - Ain Shams University
Verma, Ishwar Chander
India, New Delhi
Sir Ganga Ram Hospital
Nair, Sreelata
India, Pathanamthitta
Lifeline Super Specialty Hospital
Turner, Emily H.
United States, Seattle
University of Washington
Smith, Joshua D.
United States, Seattle
University of Washington
Jarvik, Gail Pairitz
United States, Seattle
University of Washington
Byers, Peter H.
United States, Seattle
University of Washington
Statistics
Citations: 187
Authors: 15
Affiliations: 7
Identifiers
Doi:
10.1016/j.ajhg.2013.02.009
ISSN:
00029297
e-ISSN:
15376605
Research Areas
Cancer
Genetics And Genomics
Noncommunicable Diseases