title: Frontotemporal dementia: from Mendelian genetics towards genome wide association studies.
abstract: Frontotemporal lobar degeneration is the most common cause of dementia of non-Alzheimer's type worldwide. It manifests, clinically, with behavioural changes and language impairment and is pathologically associated with tau- or ubiquitin-positive inclusions detected in neurons and glial cells of the frontal and temporal lobes in the brain. Genetic variations in the microtubule-associated protein tau and progranulin genes explain almost 50% of familial cases, whilst variations in TAR DNA-binding protein, charged multivescicular body protein 2B, valosin-containing protein and fused in sarcoma genes contribute to <5% of cases. The rapidly developing investigative techniques available to geneticists such as genome-wide association studies, whole-exome sequencing and, soon, whole-genome sequencing promise to contribute to the unravelling of the genetic architecture of this complex disease and, in the future, to the development of more sensitive, accurate and effective diagnostic and treatment measures.
authors: Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th St. STOP 9410, Lubbock, TX 79430, USA. raffaele.ferrari@ttuhsc.edu
authors: Raffaele
authors: R
authors: Ferrari
authors: John
authors: J
authors: Hardy
authors: Parastoo
authors: P
authors: Momeni
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D005091:Exons; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D009154:Mutation; D000077153:Progranulins; D000074405:Valosin Containing Protein; D016875:tau Proteins / Q000235:genetics
chemical_list: C503812:CHMP2B protein, human; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D016875:tau Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein