Ataxia with Oculomotor Apraxia: Clinical Genetic Characteristics and DNA Diagnosis

• Published in: Neuroscience and behavioral physiology Vol. 43; no. 9; pp. 1143 - 1149
• Main Authors: Rudenskaya, G. E., Kurkina, M. V., Zakharova, E. Yu
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.11.2013; Springer Nature B.V
• Subjects: Apraxia; Ataxia; Behavioral Sciences; Biomedical and Life Sciences; Biomedicine; Disease; Dysarthria; Genetics; Laboratories; Metabolic disorders; Mutation; Neurobiology; Neurosciences; Patients; Vitamin E; Israel; inherited diseases; DNA diagnosis; ataxia with oculomotor apraxia
• ISSN: 0097-0549; 1573-899X
• DOI: 10.1007/s11055-013-9863-4

Ataxia with oculomotor apraxia (AOA) is a subgroup of the autosomal recessive ataxias with a characteristic oculomotor apraxia: difficulty in transferring and fixing gaze, inability to direct the eyes to a specified side, not due to muscle weakness. Types AOA1 (the APTX gene) and the relatively frequent AOA2 (the SETX gene) are known, along with the recently (2012) described AOA3 (the PIK3R5 gene). Oculomotor apraxia is also characteristic of Louis–Bar ataxia telangiectasia and its variants. DNA diagnosis of AOA1 and AOA2 has been initiated in the Laboratory of Inherited Metabolic Diseases, Medical Genetics Scientific Center. Clinically typical AOA2 in a patient aged 25 years is described – this is the first Russian case confirmed by DNA analysis. The SETX gene was found to contain a previously undescribed mutation, c.2623-2626 del 4, leading to a frameshift mutation, in the heterozygous state; detection of a single mutation with a corresponding clinical picture is sufficient to confirm the diagnosis; the search for the allelic mutation is under way. The diagnosis was made after seven years, though the inherited nature of the disease was proposed from the very beginning. AOA1 was also confirmed in a 15-year-old patient (not investigated clinically by ourselves): two new mutations were found in the compound heterozygotic state; diagnosis of this early form was also delayed. AOA and oculomotor apraxia, which requires specific detection, are probably underestimated in clinical practice. Timely detection and molecular genetic verification would permit effective medical genetic intervention.