title: The identification of MAFB mutations in eight patients with multicentric carpo-tarsal osteolysis supports genetic homogeneity but clinical variability.
abstract: 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.
authors: Département de génétique, INSERM U781, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades, Paris, France.
authors: Cybel
authors: C
authors: Mehawej
authors: Jean-Benoît
authors: JB
authors: Courcet
authors: Geneviève
authors: G
authors: Baujat
authors: Richard
authors: R
authors: Mouy
authors: Marion
authors: M
authors: Gérard
authors: Isabelle
authors: I
authors: Landru
authors: Morgane
authors: M
authors: Gosselin
authors: Philippe
authors: P
authors: Koehrer
authors: Christiane
authors: C
authors: Mousson
authors: Sylvain
authors: S
authors: Breton
authors: Pierre
authors: P
authors: Quartier
authors: Martine
authors: M
authors: Le Merrer
authors: Laurence
authors: L
authors: Faivre
authors: Valérie
authors: V
authors: Cormier-Daire
mesh_terms: D000293:Adolescent; D000328:Adult; D002348:Carpal Bones / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D059472:Exome; D005260:Female; D031845:Hajdu-Cheney Syndrome / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D051258:MafB Transcription Factor / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D013639:Tarsal Bones / Q000503:physiopathology*
chemical_list: C490407:MAFB protein, human; D051258:MafB Transcription Factor
keywords: MAFB; osteolysis; renal disease; variability