Spinocerebellar ataxias 8, 12 and 14 in Turkey: molecular bases and genetic analyses

Abstract

Spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous groupof neurodegenerative disorders that are inherited in an autosomal dominant manner. Sincethe clinical symptoms of SCA subtypes significantly overlap, and since there is a high clinical variation even in each SCA subtype, genetic analysis is required for differentialdiagnosis. The prevalence of SCA subtypes differs among populations, thus geneticanalysis is directed based on the population-specific SCA prevalence. This studyinvestigates the distribution of SCA8, SCA12 and SCA14 in Turkish patients, who were previously screened for the six more common SCAs (SCA1, 2, 3, 6, 7 and 17). Molecularanalyses of SCA8 and SCA12 were performed both in SCA patients and in healthycontrols by PCR, followed by GeneScan analysis. SCA8 analysis was performed only forscientific purposes because of its unclear molecular basis. SCA patients and healthy controls were shown to have no expanded SCA8 and SCA12 alleles. Trinucleotide repeatnumbers of SCA8 could be determined in 59 SCA patients and in 60 healthy controls;SCA12 alleles were defined in 92 SCA patients and in 89 healthy controls. The repeatnumbers of SCA patients and healthy controls at SCA 8 and SCA12 loci were found to bein the normal ranges. SCA8 analysis was also performed in PD, AD, HD, FA, SCA1 andSCA2 patients to assist in understanding the complex molecular basis of SCA8. In contrastto the above results, expanded SCA8 alleles were found in one PD, one AD, and one FApatient, including her heterozygous father and her two sisters. The finding of expandedSCA8 alleles in control patient groups questions the disease-causing character of CTG repeat expansion. Finally, exon 4 of the PRKCG, which is responsible for SCA14, wasscreened in SCA patients. DNA sequencing results revealed that the SCA patientsexamined within the framework of this thesis have no mutation or polymorphism in this region.