Multicentric carpotarsal osteolysis is caused by mutations clustering in the amino-terminal transcriptional activation domain of MAFB.

Details

Serval ID
serval:BIB_E0478DDFD428
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Multicentric carpotarsal osteolysis is caused by mutations clustering in the amino-terminal transcriptional activation domain of MAFB.
Journal
American Journal of Human Genetics
Author(s)
Zankl A., Duncan E.L., Leo P.J., Clark G.R., Glazov E.A., Addor M.C., Herlin T., Kim C.A., Leheup B.P., McGill J., McTaggart S., Mittas S., Mitchell A.L., Mortier G.R., Robertson S.P., Schroeder M., Terhal P., Brown M.A.
ISSN
1537-6605 (Electronic)
ISSN-L
0002-9297
Publication state
Published
Issued date
2012
Volume
90
Number
3
Pages
494-501
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia characterized by aggressive osteolysis, particularly affecting the carpal and tarsal bones, and is frequently associated with progressive renal failure. Using exome capture and next-generation sequencing in five unrelated simplex cases of MCTO, we identified previously unreported missense mutations clustering within a 51 base pair region of the single exon of MAFB, validated by Sanger sequencing. A further six unrelated simplex cases with MCTO were also heterozygous for previously unreported mutations within this same region, as were affected members of two families with autosomal-dominant MCTO. MAFB encodes a transcription factor that negatively regulates RANKL-induced osteoclastogenesis and is essential for normal renal development. Identification of this gene paves the way for development of novel therapeutic approaches for this crippling disease and provides insight into normal bone and kidney development.
Keywords
Base Sequence, Carpal Bones/abnormalities, Child, Child, Preschool, Cluster Analysis, Exome, Exons, Female, Hajdu-Cheney Syndrome/genetics, Heterozygote, Humans, MafB Transcription Factor/genetics, Male, Molecular Sequence Data, Mutation, Missense, Polymorphism, Single Nucleotide, Protein Structure, Tertiary, Sequence Analysis, DNA/methods, Tarsal Bones/abnormalities, Transcriptional Activation
Pubmed
Web of science
Open Access
Yes
Create date
14/02/2013 11:19
Last modification date
20/08/2019 17:04
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