Autosomal Recessive Ataxia Caused by Three Distinct Gene Defects in a Single Consanguineous Family

Abstract

Autosomal recessive cerebellar ataxias are a group of clinically and genetically heterogeneous neurodegenerative disorders. Growing data have shown that there is difficulty with genetic counseling in a deeply consanguineous population because of the presence of genetic heterogeneity in patients sharing similar phenotypes. The objective of this study was to report on 11 Tunisian patients belonging to the same large consanguineous family and sharing autosomal recessive ataxia phenotypes caused by three distinct gene defects. A large consanguineous Tunisian family with 11 affected patients was selected. All patients had a complete neurological examination. Blood samples were collected for molecular study. Mutation analysis revealed the presence of three distinct gene defects in the FXN (FRDA), TTPA (AVED), and SACS (ARSACS) genes within the same large family. The genetic heterogeneity observed in this family drew attention to the difficulty of genetic counseling in an inbred population and to the need for genotyping all affected members before giving genetic counseling.

Keywords:

• FRDA
• AVED
• ARSACS
• Genetic heterogeneity
• Novel mutation