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The identification of MAFB mutations in eight patients with multicentric carpo–tarsal osteolysis supports genetic homogeneity but clinical variability
Author(s) -
Mehawej Cybel,
Courcet JeanBenoît,
Baujat Geneviève,
Mouy Richard,
Gérard Marion,
Landru Isabelle,
Gosselin Morgane,
Koehrer Philippe,
Mousson Christiane,
Breton Sylvain,
Quartier Pierre,
Le Merrer Martine,
Faivre Laurence,
CormierDaire Valérie
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36151
Subject(s) - missense mutation , osteolysis , exome sequencing , biology , genetic heterogeneity , genetics , skeletal disorder , bioinformatics , medicine , pathology , gene , mutation , phenotype , surgery , osteoporosis
Multicentric carpo–tarsal osteolysis (MCTO) with or without nephropathy is a rare osteolysis disorder beginning in early childhood and involving mainly carpal and tarsal bones. Renal disease appears later in life in the majority of cases and evolves quickly to end stage renal failure. Autosomal dominant (AD) inheritance has been demonstrated, with a high frequency of sporadic cases. Recently, mutations in a highly conserved region of the MAFB gene (v‐maf musculoaponeurotic fibrosarcoma oncogene ortholog B) have been identified in MCTO patients by exome sequencing. MafB, known as a regulator of various developmental processes, is essential for osteoclastogenesis and renal development. We report here the molecular screening of MAFB in eight MCTO patients from six families. We identified MAFB mutations in all, including three novel missense mutations clustering within the hot spot mutation region. Among the eight patients, six only presented renal disease. Our report confirms the genetic homogeneity of MCTO and provides data underlying the clinical variability of this disorder. © 2013 Wiley Periodicals, Inc.