Journal of Neurology

, Volume 257, Issue 12, pp 2032–2036 | Cite as

CHMP2B mutations are rare in French families with frontotemporal lobar degeneration

  • Mustapha Ghanim
  • Léna Guillot-Noel
  • Florence Pasquier
  • Ludmila Jornea
  • Vincent Deramecourt
  • Bruno Dubois
  • Isabelle Le Ber
  • Alexis Brice
  • The French Research Network on FTD and FTD/MND
Original Communication

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.

Keywords

CHMP2B FTLD ALS MND ESCRT-III 

Supplementary material

415_2010_5655_MOESM1_ESM.doc (84 kb)
Supplementary material 1 (DOC 83 kb)
415_2010_5655_MOESM2_ESM.doc (342 kb)
Supplementary material 2 (DOC 342 kb)

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Mustapha Ghanim
    • 1
  • Léna Guillot-Noel
    • 1
  • Florence Pasquier
    • 2
  • Ludmila Jornea
    • 1
  • Vincent Deramecourt
    • 2
  • Bruno Dubois
    • 1
    • 3
    • 4
    • 5
  • Isabelle Le Ber
    • 1
    • 3
    • 4
  • Alexis Brice
    • 1
    • 3
    • 4
    • 5
    • 6
    • 7
  • The French Research Network on FTD and FTD/MND
  1. 1.CRicm INSERM UMRS_975ParisFrance
  2. 2.Department of Neurology and EA2691University HospitalLilleFrance
  3. 3.Centre de Référence des démences raresHôpital de la Pitié-SalpêtrièreParisFrance
  4. 4.Département des maladies du système nerveuxAP-HP, Hôpital de la Pitié-SalpêtrièreParisFrance
  5. 5.UPMC Paris06, UMR_S679ParisFrance
  6. 6.Département de Génétique et CytogénétiqueAP-HP, Hôpital de la Pitié-SalpêtrièreParisFrance
  7. 7.CR-ICM UMR_S 975, Hôpital de la SalpêtrièreParis Cedex 13France

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