title: Novel missense mutation in charged multivesicular body protein 2B in a patient with frontotemporal dementia.
abstract: Frontotemporal dementia (FTD) is the second major cause of dementia in persons below the age of 65 years after Alzheimer disease. FTD is clinically, pathologically, and genetically heterogeneous and has been associated with mutations in different genes located on chromosomes 17, 9, and 3. In our study we report a novel heterozygous g.26218G>A variant in exon 6 of charged multivesicular body protein 2B (CHMP2B), predicted to cause the amino acid change p.Ser187Asn, in one patient diagnosed with FTD. We were not able to determine the mode of inheritance of the mutation as we did not have access to the genetically informative family members of the proband; those who were screened did not carry the variant. We did not find this variant in 273 White controls although we did find it in 6 of 94 African-American controls. Most of the mutations in CHMP2B which are considered pathogenic lead to partial deletion of the C-terminus region of CHMP2B protein. Based on previous reports and on our current data, missense mutations in this gene seem unlikely to be pathogenic. The pathogenicity of CHMP2B mutations requires further investigation.
authors.affiliation: *Departments of Internal Medicine ♯Pharmacology and Neuroscience, Health Sciences Center, Texas Tech University, Lubbock, TX ∥Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke Building ¶Laboratory of Neurogenetics, National Institute on Aging, National Institute of Health, Bethesda ‡National Institutes of Health (NIH), National Institute on Aging (NIA), Clinical Research Branch, Baltimore, MD §Litwin-Zucker Center for Research on Alzheimer's Disease and Memory Disorders, North Shore/Long, Island Jewish Healthcare System, Manhasset, NY †Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, UCL, London, England.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferrari
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kapogiannis
authors.forename: Edward D
authors.initials: ED
authors.lastname: Huey
authors.forename: Jordan
authors.initials: J
authors.lastname: Grafman
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Parastoo
authors.initials: P
authors.lastname: Momeni
mesh_terms: D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics*; D005190:Family; D057180:Frontotemporal Dementia / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*
chemical_list: C503812:CHMP2B protein, human; D056827:Endosomal Sorting Complexes Required for Transport