An incompletely penetrant novel MAFB (p.Ser56Phe) variant in autosomal dominant multicentric carpotarsal osteolysis syndrome

Dworschak,Gabriel  C.; Draaken,Markus; Hilger,Alina; Born,Mark; Reutter,Heiko; Ludwig,Michael

doi:10.3892/ijmm.2013.1373

An incompletely penetrant novel MAFB (p.Ser56Phe) variant in autosomal dominant multicentric carpotarsal osteolysis syndrome

Authors:
- Gabriel C. Dworschak
- Markus Draaken
- Alina Hilger
- Mark Born
- Heiko Reutter
- Michael Ludwig
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Affiliations: Institute of Human Genetics, University Hospital of Bonn, D-53127 Bonn, Germany, Department of Pediatric Radiology, Children's Hospital, University Hospital of Bonn, D-53127 Bonn, Germany, Department of Clinical Chemistry and Clinical Pharmacology, University Hospital of Bonn, D-53127 Bonn, Germany
Published online on: May 10, 2013 https://doi.org/10.3892/ijmm.2013.1373
Pages: 174-178

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Abstract

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.

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