An incompletely penetrant novel MAFB (p.Ser56Phe) variant in autosomal dominant multicentric carpotarsal osteolysis syndrome
| Autor: | Heiko Reutter, Gabriel C. Dworschak, Markus Draaken, Alina C. Hilger, Mark Born, Michael Ludwig |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Osteolysis Adolescent Genetic counseling MafB Transcription Factor Molecular Sequence Data Mutation Missense Penetrance Biology Genetics medicine Humans Missense mutation Amino Acid Sequence Epigenetics Base Sequence Genetic Variation General Medicine medicine.disease Phenotype Pedigree Radiography Hand Bones MAFB Dysplasia Cancer research Sequence Alignment |
| Zdroj: | International Journal of Molecular Medicine. 32:174-178 |
| ISSN: | 1791-244X 1107-3756 |
| DOI: | 10.3892/ijmm.2013.1373 |
| Popis: | Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare autosomal dominant skeletal dysplasia usually presenting in early childhood with variable phenotypic features and course. Clinical manifestations comprise aggressive osteolysis of the carpal and tarsal bones in particular, an often progressive nephropathy leading to end-stage renal disease, craniofacial anomalies and mental impairment. Recently, heterozygous missense mutations in the V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) (MAFB) gene have been causally related to MCTO patients in 13 unrelated families investigated. Contrary to these findings suggesting complete penetrance, in the present study, we identified a novel missense MAFB variant present not only in the patient, but also in his unaffected mother, sister and maternal grandmother. This observation demonstrates an incomplete penetrance for some MAFB mutations, thereby suggesting that modifier genes, epigenetic mechanisms or environmental factors may modulate the MCTO phenotype. This should be considered in diagnosis and genetic counseling. |
| Databáze: | OpenAIRE |
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