Ataxia with Impaired DNA Repair in Adults: A Case Series and Review of the Literature

Introduction. Ataxia with impaired DNA repair is a group of inherited diseases with a wide range of neurological and extraneural manifestations. There are some difficulties in the differential diagnosis of this group of ataxias due to significant clinical polymorphism. Objective. To analyze the clinical presentation, laboratory and instrumental examinations data of a series of genetically confirmed cases of ataxia with impaired DNA repair in adult patients. Material and methods. 55 patients with ataxia of degenerative origin were examined. Clinical evaluation, nerve velocity study, brain MRI, alpha-fetoprotein, immunoglobulins, cholesterol and albumin, creatine phosphokinase activity were performed. Massive parallel sequencing (MPS) was used for genotyping, including the original multigene panel. Results. 8 (14.5%) patients with various forms of ataxia with impaired DNA repair were verified: 5 patients with ataxia-telangiectasia, 3 — with ataxia with oculomotor apraxia types 1 and 2. The clinical features of this forms are characterized, the prevalence of atypical forms of ataxia-telangiectasia in a sample of Russian adult patients is revealed. Phenotypes of ataxia with oculomotor apraxia of the 1 and 2 types corresponded to the classical presentation. Several identified mutations in the ATM and SETX genes are described for the first time. Conclusion. Ataxia with impaired DNA repair is a common group of ataxias in adult Russian patients. They are represented by ataxia-telangiectasia, ataxia with oculomotor apraxia types 1 and 2, often due to new mutations. MPS is the method of choice for genotyping of these forms of ataxia.

DNA repair disorders, ataxia telangiectasia, ataxia with oculomotor apraxia, clinical presentation, genetic diagnosis

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