title: A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy.
abstract: BACKGROUND
  Neurodegeneration with brain iron accumulation is clinically and genetically heterogeneous because of mutations in at least 7 nuclear genes.
  
  
  METHODS
  We performed homozygosity mapping and whole-exome sequencing in 2 brothers with brain iron accumulation from a consanguineous family.
  
  
  RESULTS
  We identified a homozygous missense mutation in both brothers in the very recently identified chromosome 19 open-reading frame 12 gene. The disease presented before age 10 with slowly progressive tremor, dystonia, and spasticity. Additional features were optic atrophy, peripheral neuropathy, and learning difficulties. A raised serum creatine kinase indicated neuromuscular involvement, and compensatory mitochondrial proliferation implicated mitochondrial dysfunction as a pathological mechanism.
  
  
  CONCLUSIONS
  Further studies are needed to explore the function of the chromosome 19 open-reading frame 12 gene, and extended genetic analysis on larger patient cohorts will provide more information about the presentation and frequency of this disease.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. rita.horvath@ncl.ac.uk
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
authors.forename: Elke
authors.initials: E
authors.lastname: Holinski-Feder
authors.forename: Vivienne C M
authors.initials: VC
authors.lastname: Neeve
authors.forename: Angela
authors.initials: A
authors.lastname: Pyle
authors.forename: Helen
authors.initials: H
authors.lastname: Griffin
authors.forename: Deephthi
authors.initials: D
authors.lastname: Ashok
authors.forename: Charlotte
authors.initials: C
authors.lastname: Foley
authors.forename: Gavin
authors.initials: G
authors.lastname: Hudson
authors.forename: Bernd
authors.initials: B
authors.lastname: Rautenstrauss
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nürnberg
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Jörg
authors.initials: J
authors.lastname: Kortler
authors.forename: Birgit
authors.initials: B
authors.lastname: Neitzel
authors.forename: Ingelore
authors.initials: I
authors.lastname: Bässmann
authors.forename: Thahira
authors.initials: T
authors.lastname: Rahman
authors.forename: Bernard
authors.initials: B
authors.lastname: Keavney
authors.forename: John
authors.initials: J
authors.lastname: Loughlin
authors.forename: Sophie
authors.initials: S
authors.lastname: Hambleton
authors.forename: Benedikt
authors.initials: B
authors.lastname: Schoser
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Mauro
authors.initials: M
authors.lastname: Santibanez-Koref
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D000293:Adolescent; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002648:Child; D003241:Consanguinity; D020821:Dystonic Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D020125:Mutation, Missense; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009896:Optic Atrophy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013577:Syndrome
chemical_list: D007501:Iron