Molecular Basis of Friedreich Ataxia: DNA Analysis and Diagnosis in Turkish Patients

Abstract

Friedreich Ataxia (FA) is an autosomal recessive neurodegenerative disease with onset in childhood, followed by an uninterrupted course that terminates with death in the la test fifth decade of life. FA's estimated carrier prevalence is about one in 110, and it affects about one in 50,000 people, making it the most common inherited ataxia in the Caucasian population. The FRDA gene was mapped to the 9q13-21.1 region in 1996. The encoded protein of 210 amino acids, called frataxin, localizes to mitochondria, and plays a crucial role in iron sulfur cluster biosynthesis. FA is due to a deficiency in frataxin, caused predominantly, by a GAA triplet-repeat expansion within the first intron of the FRDA gene. The decrease in frataxin transcription and expression leads to a decrease in iron sulfur cluster-containing proteins, causing production of free radicals. In the framework of a project on neurodegenerative disorders conducted at Boğaziçi University, Molecular Biology and Genetics Department, a reliable and reproducible polymerase chain reaction protocol has been optimized in our laboratory; applying this method, 153 Turkish individuals, patients and their families, have been screened fara GAA triplet-repeat expansion. Among them, 38 were found to be homozygous far the expansion, and 46 were heterozygote carriers. Since 1996, year of elucidation of the genetic cause of Friedreich Ataxia, serious advances have been made in understanding its pathogenesis. There is every reason to expect that effective strategies will be developed in the near future to overcome the consequences of reduced frataxin expression.