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

Zankl, A., Duncan, Emma 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, Matthew A. (2012) Multicentric carpotarsal osteolysis is caused by mutations clustering in the amino-terminal transcriptional activation domain of MAFB. American Journal of Human Genetics, 90(3), pp. 494-501.

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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.

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ID Code: 87703
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Additional URLs:
Keywords: osteoclast differentiation factor, transcription factor MafB, amino terminal sequence, article, base pairing, bone dysplasia, exome, exon, gene identification, gene mutation, gene sequence, heterozygote, human, kidney development, missense mutation, multicentric carpotarsal osteolysis, osteoclastogenesis, priority journal, protein domain, transcription initiation, Base Sequence, Carpal Bones, Child, Child, Preschool, Cluster Analysis, Exons, Female, Hajdu-Cheney Syndrome, Humans, MafB Transcription Factor, Male, Molecular Sequence Data, Mutation, Missense, Polymorphism, Single Nucleotide, Protein Structure, Tertiary, Sequence Analysis, DNA, Tarsal Bones, Transcriptional Activation
DOI: 10.1016/j.ajhg.2012.01.003
ISSN: 0002-9297
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Elsevier (Cell Press)
Deposited On: 24 Sep 2015 02:09
Last Modified: 21 Mar 2016 23:32

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