targeted next-generation sequencing revealed novel mutations in iranian ataxic patients

hereditary ataxias are heterogeneous group of neurodegenerative disorders classified mainly into more than 40 autosomal dominant cerebellar ataxias and 50 recessive ataxias. large amount of nearly uncommon subtypes with extensive phenotypic overlap and relatively high rate of abnormal repetitive sequence expansions, such as trinucleotide repeat expansions make diagnostic genetic testing complicated. here we used targeted next generation sequencing on unrelated ataxias probands for whom commonly known spinocerebellar ataxias (scas) caused by trinucleotide repeat expansions including  1, 2, 3, 6, 7 and 17 and friedreich ataxia have been excluded based on in-house testing strategy. all the cases were recruited from individuals referred to kariminezhad-najmabadi center in tehran, iran between 2015-2016. we performed targeted capture on a total of 50 genes considered to be appropriate candidates for ataxia. variants detected through next generation sequencing (ngs) were confirmed and co-segregated through sanger sequencing. from 8 unrelated ataxia patients that referred to our center, genetic testing revealed a total of 5 mutations in the 4 investigated patients, from which 4 were novel variants and 1 has been previously published as a pathogenic variant.  our pathogenicity interpretation pathway detected five different mutations in three different genes comprising sacs, atm, and ttpa. of which, we identified two frameshift variants in sacs and ttpa genes, one nonsense variant in atm gene and a splice site variant and a missense variant in atm gene in a compound heterozygote state and a known missense variant in atm gene. considering the exact preliminary clinical diagnosis and excluding the possibility of repeat expansions, it seems that targeted next generation sequencing would be a promising method for molecular detection in hereditary ataxia.