title: CHMP2B mutations are rare in French families with frontotemporal lobar degeneration.
abstract: Two C-truncating CHMP2B (chromatin modifying protein 2B) mutations were recently found in Danish and Belgian families with autosomal dominant forms of frontotemporal lobar degeneration (FTLD). In addition, few CHMP2B missense mutations of uncertain pathogenic role were reported in several families with FTLD or FTLD associated with motoneuron disease (FTLD-MND). In order to determine the genetic contribution of CHMP2B mutations in FTLD and FTLD-MND families, we analyzed the CHMP2B gene in 198 French probands with familial FTLD and FTLD-MND. One CHMP2B missense variant was found in a proband with familial FTLD (0.8%). The pathogenic role of CHMP2B missense variants is unclear, however the pSer194Leu substitution, located in the C-terminal domain of the protein, was predicted to alter the stability of the protein by in silico analyses. We conclude that CHMP2B mutations represent a rare cause of familial FTLD and they are not implicated in familial FTLD-MND in French patients. The previously reported C-truncating CHMP2B mutations may be private to the Danish and Belgian pedigrees.
authors.affiliation: CRicm INSERM UMRS_975, 75013, Paris, France.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Ghanim
authors.forename: Léna
authors.initials: L
authors.lastname: Guillot-Noel
authors.forename: Florence
authors.initials: F
authors.lastname: Pasquier
authors.forename: Ludmila
authors.initials: L
authors.lastname: Jornea
authors.forename: Vincent
authors.initials: V
authors.lastname: Deramecourt
authors.forename: Bruno
authors.initials: B
authors.lastname: Dubois
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Ber
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010641:Phenotype
chemical_list: C503812:CHMP2B protein, human; D056827:Endosomal Sorting Complexes Required for Transport