Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts

Michael C. Kruer, Reema Paudel, Wendy Wagoner, Lynn Sanford, Eleanna Kara, Allison Gregory, Tom Foltynie, Andrew Lees, Kailash Bhatia, John Hardy, Susan Hayflick, Henry Houlden

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)35-38
Number of pages4
JournalNeuroscience Letters
Volume523
Issue number1
DOIs
StatePublished - Aug 8 2012

Fingerprint

Dystonia
Parkinsonian Disorders
Mutation
Putamen
Computer Simulation
Genes
Iron
Neurodegeneration with brain iron accumulation (NBIA)
Genome

Keywords

  • Iron
  • Kufor Rakeb, ATP13A2, Dystonia
  • NBIA
  • Neurodegeneration
  • Parkinsonism

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts. / Kruer, Michael C.; Paudel, Reema; Wagoner, Wendy; Sanford, Lynn; Kara, Eleanna; Gregory, Allison; Foltynie, Tom; Lees, Andrew; Bhatia, Kailash; Hardy, John; Hayflick, Susan; Houlden, Henry.

In: Neuroscience Letters, Vol. 523, No. 1, 08.08.2012, p. 35-38.

Research output: Contribution to journalArticle

Kruer, MC, Paudel, R, Wagoner, W, Sanford, L, Kara, E, Gregory, A, Foltynie, T, Lees, A, Bhatia, K, Hardy, J, Hayflick, S & Houlden, H 2012, 'Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts', Neuroscience Letters, vol. 523, no. 1, pp. 35-38. https://doi.org/10.1016/j.neulet.2012.06.036
Kruer, Michael C. ; Paudel, Reema ; Wagoner, Wendy ; Sanford, Lynn ; Kara, Eleanna ; Gregory, Allison ; Foltynie, Tom ; Lees, Andrew ; Bhatia, Kailash ; Hardy, John ; Hayflick, Susan ; Houlden, Henry. / Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts. In: Neuroscience Letters. 2012 ; Vol. 523, No. 1. pp. 35-38.
@article{7fed715dfae84ba483f23246968f4603,
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.",
keywords = "Iron, Kufor Rakeb, ATP13A2, Dystonia, NBIA, Neurodegeneration, Parkinsonism",
author = "Kruer, {Michael C.} and Reema Paudel and Wendy Wagoner and Lynn Sanford and Eleanna Kara and Allison Gregory and Tom Foltynie and Andrew Lees and Kailash Bhatia and John Hardy and Susan Hayflick and Henry Houlden",
year = "2012",
month = "8",
day = "8",
doi = "10.1016/j.neulet.2012.06.036",
language = "English (US)",
volume = "523",
pages = "35--38",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts

AU - Kruer, Michael C.

AU - Paudel, Reema

AU - Wagoner, Wendy

AU - Sanford, Lynn

AU - Kara, Eleanna

AU - Gregory, Allison

AU - Foltynie, Tom

AU - Lees, Andrew

AU - Bhatia, Kailash

AU - Hardy, John

AU - Hayflick, Susan

AU - Houlden, Henry

PY - 2012/8/8

Y1 - 2012/8/8

N2 - 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.

AB - 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.

KW - Iron

KW - Kufor Rakeb, ATP13A2, Dystonia

KW - NBIA

KW - Neurodegeneration

KW - Parkinsonism

UR - http://www.scopus.com/inward/record.url?scp=84864320285&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864320285&partnerID=8YFLogxK

U2 - 10.1016/j.neulet.2012.06.036

DO - 10.1016/j.neulet.2012.06.036

M3 - Article

C2 - 22743658

AN - SCOPUS:84864320285

VL - 523

SP - 35

EP - 38

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

IS - 1

ER -