title: C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis.
abstract: Mutations in C19orf12 have been recently identified as the molecular genetic cause of a subtype of neurodegeneration with brain iron accumulation (NBIA). Given the mitochondrial localization of the gene product the new NBIA subtype was designated mitochondrial membrane protein-associated neurodegeneration. Frequent features in the patients described so far included extrapyramidal signs and pyramidal tract involvement. Here, we report three C19orf12-mutant patients from two families presenting with predominant upper and lower motor neuron dysfunction mimicking amyotrophic lateral sclerosis with juvenile onset. While extrapyramidal signs were absent, all patients showed neuropsychological abnormalities with disinhibited or impulsive behavior. Optic atrophy was present in the simplex case. T2-weighted cranial MRI showed hypointensities suggestive of iron accumulation in the globi pallidi and the midbrain in all patients. Sequence analysis of C19orf12 revealed a novel mutation, p.Gly66del, compound heterozygous with known mutations in all patients. These patients highlight that C19orf12 defects should be considered as a differential diagnosis in patients with juvenile onset motor neuron diseases. Patients have to be examined carefully for neuropsychological abnormalities, optic neuropathy, and signs of brain iron accumulation in MRI.
authors.affiliation: Department of Neurology, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06097, Halle (Saale), Germany. marcus.deschauer@medizin.uni-halle.de
authors.forename: M
authors.initials: M
authors.lastname: Deschauer
authors.forename: C
authors.initials: C
authors.lastname: Gaul
authors.forename: C
authors.initials: C
authors.lastname: Behrmann
authors.forename: H
authors.initials: H
authors.lastname: Prokisch
authors.forename: S
authors.initials: S
authors.lastname: Zierz
authors.forename: T B
authors.initials: TB
authors.lastname: Haack
mesh_terms: D000293:Adolescent; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics; D001921:Brain / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D019189:Iron Metabolism Disorders / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D019150:Neuroaxonal Dystrophies / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult
chemical_list: C568481:C19orf12 protein, human; D024101:Mitochondrial Proteins