title: Analysis of the C19orf12 and WDR45 genes in patients with neurodegeneration with brain iron accumulation.
abstract: BACKGROUND
  Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of diseases presenting with movement disorders and brain iron deposits. In addition to NBIA subtypes caused by mutations in PANK2 and PLA2G6, mutations in the C19orf12 gene were recently described as the third frequent cause of NBIA (called mitochondrial membrane protein-associated neurodegeneration, MPAN). Additionally, the X-linked gene WDR45 was found causative for a special subtype named static encephalopathy in childhood with neurodegeneration in adulthood (also called BPAN); however, analysis of this gene in a broader spectrum of NBIA has not been reported yet.
  
  
  METHODS
  In a heterogeneous cohort of 69 patients with suspected NBIA that did not carry mutations in PANK2 and PLA2G6, the coding region of C19orf12 was evaluated by Sanger sequencing. The WDR45 gene was analyzed via high resolution melting and subsequent sequence analysis.
  
  
  RESULTS
  Previously described homozygous C19orf12 mutations were found in 3/69 NBIA patients (4.3%). Analysis of the WDR45 gene revealed a novel heterozygous missense mutation in one female NBIA patient showing psychomotor retardation with secondary decline.
  
  
  CONCLUSIONS
  C19orf12 mutations were confirmed in our heterogeneous NBIA cohort, while WDR45 mutations appear to be restricted to the subtype showing encephalopathy in childhood with neurodegeneration in adulthood.
authors.affiliation: Department of Human Genetics, Ruhr-University, Bochum, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Tschentscher
authors.affiliation: Department of Human Genetics, Ruhr-University, Bochum, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Dekomien
authors.affiliation: Pediatric Neurology, Children's Hospital Erlangen, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Ross
authors.affiliation: Department of Human Genetics, University of Bonn, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Cremer
authors.affiliation: Department of Radiology, University of Bonn, Germany.
authors.forename: Guido M
authors.initials: GM
authors.lastname: Kukuk
authors.affiliation: Department of Human Genetics, Ruhr-University, Bochum, Germany; Faculty of Health, University Witten/Herdecke, Witten, Germany.
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Epplen
authors.affiliation: Department of Human Genetics, Ruhr-University, Bochum, Germany. Electronic address: sabine.hoffjan@ruhr-uni-bochum.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoffjan
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D054522:Group VI Phospholipases A2 / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D020125:Mutation, Missense; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C578284:WDR45 protein, human; D007501:Iron; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human
keywords: BPAN; C19orf12; MPAN; Mutation analysis; NBIA; WDR45