New Insights Into Different Cerebellar Ataxia Forms

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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An international research team has recently published in the journal BMC Medical Genetics a large cohort analysis of Algerian patients with different forms of ataxia. The study is entitled “Molecular and clinical study of a cohort of 110 Algerian patients with autosomal recessive ataxia”.

Ataxia is defined as a neurological sign characterized by the lack of voluntary coordination of muscle movements. Individuals with this medical condition experience impairment in coordination and balance. In cases where only the cerebellum is affected the condition is called cerebellar ataxia. Autosomal recessive cerebellar ataxias (ARCA) correspond to a group of neurodegenerative disorders with a great genetic and phenotypic heterogeneity. More than 30 genes or loci have been linked to the development of more than 20 different ARCA conditions. An accurate disease diagnosis of the ARCA type is therefore required in order to provide proper care.

In the study, researchers analyzed 110 patients (76 families) in several hospitals in Algeria with a cerebellar ataxia phenotype linked to an autosomal recessive pattern of inheritance. Blood samples were collected from all patients and genomic DNA extracted to perform mutational screening and sequencing of specific genes linked to inherited cerebellar ataxia phenotypes.

Researchers found 23 different mutations, including 6 new ones, and 9 different types of ARCA present in the patient cohort analyzed. The most common ARCA type in this cohort was Friedreich’s ataxia, which was identified in 49 patients (31 families). Friedreich’s ataxia is a rare inherited neurodegenerative disease characterized by progressive damage of the nervous system with degeneration of the spinal cord and peripheral nerves that leads to muscle weakness, sensory loss, balance deficits and lack of voluntary coordination of muscle movements. The disease is caused by a mutation in a gene called frataxin (FXN) that leads to a defective expression of the frataxin protein. Disease onset is usually during childhood or adolescence and the disorder leads to progressive disability, dependence on a wheelchair and reduced life expectancy. All the Friedreich’s ataxia patients in the Algerian cohort had mutations in the FXN gene.

Apart from the most common mutations and ataxia forms, researchers also found rarer or underdiagnosed forms that might have been underestimated, such as spinocerebellar ataxia autosomal recessive 8 and 9 (SCAR8, SCAR9), Marinesco-Sjögren syndrome (MSS), ataxia with oculomotor aparaxia type 1 (AOA1) and polyneupathy, hearing loss, ataxia, retinitis pigmentosa and cataract (PHARC).

The team concluded that the main ARCA type present in the Algerian patient cohort analyzed was Friedreich’s ataxia. They further suggest that epidemiological studies should be conducted to refine the genotype/phenotype correlation in the different ARCA conditions and establish a more accurate and detailed clinical characterization of each one.