title: Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts.
abstract: Several causative genes have been identified for both dystonia-parkinsonism and neurodegeneration with brain iron accumulation (NBIA), yet many patients do not have mutations in any of the known genes. Mutations in the ATP13A2 lead to Kufor Rakeb disease, a form of autosomal recessive juvenile parkinsonism that also features oromandibular dystonia. More recently, evidence of iron deposition in the caudate and putamen have been reported in patients with ATP13A2 mutations. We set out to determine the frequency of ATP13A2 mutations in cohorts of idiopathic NBIA and dystonia-parkinsonism. We screened for large deletions using whole genome arrays, and sequenced the entire coding region in 92 cases of NBIA and 76 cases of dystonia-parkinsonism. A number of coding and non-coding sequence variants were identified in a heterozygous state, but none were predicted to be pathogenic based on in silico analyses. Our results indicate that ATP13A2 mutations are a rare cause of both NBIA and dystonia-parkinsonism.
authors: Sanford Children's Health Research Center, Sioux Falls, SD 57104, USA. michael.kruer@sanfordhealth.org
authors: Michael C
authors: MC
authors: Kruer
authors: Reema
authors: R
authors: Paudel
authors: Wendy
authors: W
authors: Wagoner
authors: Lynn
authors: L
authors: Sanford
authors: Eleanna
authors: E
authors: Kara
authors: Allison
authors: A
authors: Gregory
authors: Tom
authors: T
authors: Foltynie
authors: Andrew
authors: A
authors: Lees
authors: Kailash
authors: K
authors: Bhatia
authors: John
authors: J
authors: Hardy
authors: Susan J
authors: SJ
authors: Hayflick
authors: Henry
authors: H
authors: Houlden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D015897:Comorbidity; D020821:Dystonic Disorders / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D054522:Group VI Phospholipases A2 / Q000172:deficiency / Q000235:genetics; D006801:Humans; D038622:Internationality; D019189:Iron Metabolism Disorders / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D019150:Neuroaxonal Dystrophies / Q000453:epidemiology* / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D006180:Proton-Translocating ATPases / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: C514983:ATP13A2 protein, human; D005819:Genetic Markers; D054522:Group VI Phospholipases A2; D006180:Proton-Translocating ATPases