Premium
A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy
Author(s) -
Horvath Rita,
HolinskiFeder Elke,
Neeve Vivienne C.M.,
Pyle Angela,
Griffin Helen,
Ashok Deephthi,
Foley Charlotte,
Hudson Gavin,
Rautenstrauss PhD Bernd,
Nürnberg Gudrun,
Nürnberg Peter,
Kortler Jörg,
Neitzel Birgit,
Bäßmann Ingelore,
Rahman Thahira,
Keavney Bernard,
Loughlin John,
Hambleton Sophie,
Schoser Benedikt,
Lochmüller Hanns,
SantibanezKoref Mauro,
Chinnery Patrick F.
Publication year - 2012
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.24980
Subject(s) - atrophy , missense mutation , dystonia , neurodegeneration , exome sequencing , genetics , peripheral neuropathy , pathology , biology , mutation , medicine , neuroscience , disease , gene , endocrinology , diabetes mellitus
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. © 2012 Movement Disorder Society