title: A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease.
abstract: BACKGROUND
  Frontotemporal dementia with parkinsonism is often linked to chromosome 17 and is related to mutations in the MAPT gene. In some families the genetic basis is still unknown. The authors report two pedigrees with FTDP-17 harboring a novel mutation (K317M) in exon 11 in the MAPT gene.
  
  
  METHODS
  The authors identified two apparently unrelated pedigrees with an autosomal dominant neurodegenerative condition. Thirteen patients were examined and eight autopsies were performed.
  
  
  RESULTS
  Mean age at onset was 48 years. Mean disease duration was 6 years. Dysarthria often heralded the disease. All cases had parkinsonism and pyramidalism and half of them had amyotrophy. Behavioral or personality changes were not a prominent feature. Cognitive decline appeared late in the evolution. Neuropathologically, a massive degeneration of the substantia nigra without Lewy bodies was a constant finding. A variable degree of frontotemporal atrophy was found. Corticospinal tract degeneration and anterior horn neuron loss were present in six of seven autopsies in which the spinal cord was examined. An extensive deposition of abnormal tau protein in a mixed pattern (neuronal, glial) was observed. Pick's bodies were not seen. Biochemical analysis of tau revealed two bands of 64 and 68 kDa.
  
  
  CONCLUSIONS
  Genetic analysis revealed the same novel mutation (K317M) in exon 11 of the MAPT gene in both pedigrees. A common haplotype between members of the two pedigrees suggests that they belong to the same family.
authors.affiliation: Neurology Service, Department of Neurosciences, Hospital Cruces, University of the Basque Country, Baracaldo, Vizcaya, Spain. jjzarranz@hcru.osakidetza.net
authors.forename: J J
authors.initials: JJ
authors.lastname: Zarranz
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
authors.forename: E
authors.initials: E
authors.lastname: Lezcano
authors.forename: M I
authors.initials: MI
authors.lastname: Forcadas
authors.forename: B
authors.initials: B
authors.lastname: Eizaguirre
authors.forename: B
authors.initials: B
authors.lastname: Atarés
authors.forename: B
authors.initials: B
authors.lastname: Puig
authors.forename: J C
authors.initials: JC
authors.lastname: Gómez-Esteban
authors.forename: C
authors.initials: C
authors.lastname: Fernández-Maiztegui
authors.forename: I
authors.initials: I
authors.lastname: Rouco
authors.forename: T
authors.initials: T
authors.lastname: Pérez-Concha
authors.forename: M
authors.initials: M
authors.lastname: Fernández
authors.forename: O
authors.initials: O
authors.lastname: Rodríguez
authors.forename: A B
authors.initials: AB
authors.lastname: Rodríguez-Martínez
authors.forename: M Martínez
authors.initials: MM
authors.lastname: de Pancorbo
authors.forename: P
authors.initials: P
authors.lastname: Pastor
authors.forename: J
authors.initials: J
authors.lastname: Pérez-Tur
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004252:DNA Mutational Analysis; D003704:Dementia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005799:Genes, Dominant; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016875:tau Proteins / Q000235:genetics
chemical_list: D005819:Genetic Markers; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D016875:tau Proteins