American journal of human genetics, 2012-03, Vol.90 (3), p.494-501
2012
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- Autor(en) / Beteiligte
- Titel
- Multicentric Carpotarsal Osteolysis Is Caused by Mutations Clustering in the Amino-Terminal Transcriptional Activation Domain of MAFB
- Ist Teil von
- American journal of human genetics, 2012-03, Vol.90 (3), p.494-501
- Ort / Verlag
- Cambridge, MA: Elsevier Inc
- Erscheinungsjahr
- 2012
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0002-9297eISSN: 1537-6605DOI: 10.1016/j.ajhg.2012.01.003Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3309183
- Format
- –
- Schlagworte
- Base pairs, Base Sequence, Biological and medical sciences, Bone, Bone diseases, Bone dysplasia, Carpal Bones - abnormalities, Child, Child, Preschool, Cluster Analysis, Exome, Exons, Female, Fundamental and applied biological sciences. Psychology, General aspects. Genetic counseling, Genetics, Genetics of eukaryotes. Biological and molecular evolution, Hajdu-Cheney Syndrome - genetics, Heterozygote, Humans, Kidney, MafB Transcription Factor - genetics, Male, Medical genetics, Medical sciences, Missense mutation, Molecular and cellular biology, Molecular Sequence Data, Mutation, Mutation, Missense, Osteoclastogenesis, Osteolysis, Polymorphism, Single Nucleotide, Protein Structure, Tertiary, Renal failure, Sequence Analysis, DNA - methods, Skeleton, tarsal bone, Tarsal Bones - abnormalities, Transcription activation, Transcription factors, Transcriptional Activation