Novel AARS2 gene mutation producing leukodystrophy: a case report

AARS2 gene (NM_020745.3) mutations result in two different phenotypic diseases: infantile mitochondrial cardiomyopathy and late-onset leukoencephalopathy. The patient's first symptoms appeared at the age of 18 years with behavioral changes and psychiatric problems. Some years later, extrapyrami...

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Bibliographic Details
Published in:Journal of human genetics 2017-02, Vol.62 (2), p.329-333
Main Authors: Szpisjak, Laszlo, Zsindely, Nora, Engelhardt, Jozsef I, Vecsei, Laszlo, Kovacs, Gabor G, Klivenyi, Peter
Format: Article
Language:English
Subjects:
Adult
Alanine-tRNA Ligase - genetics
Biopsy
Cardiomyopathy
Case reports
Cognition Disorders - genetics
Cognitive ability
Extrapyramidal system
Female
Genetic analysis
Genetic screening
Genetic Testing
Humans
Leukodystrophy
Leukoencephalopathies - diagnosis
Leukoencephalopathies - genetics
Leukoencephalopathies - pathology
Leukoencephalopathy
Magnetic Resonance Imaging
Male
Mental disorders
Missense mutation
Mitochondria
Mutation
Mutation, Missense - genetics
Neuroimaging
Nystagmus
Patients
Phenotype
Phenotypes
Point mutation
Primary Ovarian Insufficiency - genetics
Substantia alba
White Matter - abnormalities
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Summary:AARS2 gene (NM_020745.3) mutations result in two different phenotypic diseases: infantile mitochondrial cardiomyopathy and late-onset leukoencephalopathy. The patient's first symptoms appeared at the age of 18 years with behavioral changes and psychiatric problems. Some years later, extrapyramidal symptoms, cognitive impairment, nystagmus, dysarthria and pyramidal symptoms also developed. The brain magnetic resonance imaging (MRI) indicated extensive white matter abnormalities. The diagnosis of AARS2 gene mutations causing leukodystrophy was confirmed by genetic testing. Segregation analysis confirmed the compound heterozygous state of the patient. Histological examination of the biopsy did not prove specific pathological alterations. The clinical phenotype of our patient was compared with seven previously described patients suffering from leukoencephalopathy caused by AARS2 mutations. We have documented a new, nonsense AARS2 gene mutation (c.578T>G, p.Leu193*) and a known missense mutation (c.595C>T, p.Arg199Cys) associated with leukoencephalopathy in a male patient. Clinical features, imaging characteristics and genetic testing are presented, and histological data from an AARS2-related leukodystrophy patient are described for the first time.
ISSN:1434-5161
1435-232X
DOI:10.1038/jhg.2016.126