title: An incompletely penetrant novel MAFB (p.Ser56Phe) variant in autosomal dominant multicentric carpotarsal osteolysis syndrome.
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.
authors.affiliation: Institute of Human Genetics, University Hospital of Bonn, D-53127 Bonn, Germany.
authors.forename: Gabriel C
authors.initials: GC
authors.lastname: Dworschak
authors.forename: Markus
authors.initials: M
authors.lastname: Draaken
authors.forename: Alina
authors.initials: A
authors.lastname: Hilger
authors.forename: Mark
authors.initials: M
authors.lastname: Born
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D014644:Genetic Variation; D050276:Hand Bones / Q000000981:diagnostic imaging; D006801:Humans; D051258:MafB Transcription Factor / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010014:Osteolysis / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D011859:Radiography; D016415:Sequence Alignment
chemical_list: D051258:MafB Transcription Factor