CHMP2B mutations are rare in French families with frontotemporal lobar degeneration
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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.
KeywordsCHMP2B FTLD ALS MND ESCRT-III
We thank Ms. Lydia Guennec, Isabelle Lagroua, and Christelle Dussert (DNA and cell bank of CR-ICM UMRS_975, Hôpital de la Salpêtrière, Paris) for their excellent technical assistance and the Dr. Sophie Rivaud-Pechoux for statistical analyses (CR-ICM UMRS_975, Hôpital de la Salpêtrière, Paris). This study was supported by ANR R6363DS (to A.B.), France Alzheimer association (to A.B), ANR R08104DS (to ILB), and ARsla (to A.B.).
Conflict of interest statement
The authors declare that they have no conflicts of interest.
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