Clinical and molecular genetic findings of hereditary Parkinson's patients from Turkey.

Abstract

IntroductionThe majority of Parkinson's disease (PD) ensue late-onset with a complex spectrum of environmental andgenetic risk factors. Awareness of genetic causes in patients with PD is essential for genetic counseling and future genotype-oriented therapeutic developments.MethodsLarge pathogenic changes in eight PD-related genes and small pathogenic sequence variants in 22 PD-related genes were investigated simultaneously in 82 PD patients from 79 families where clinical evaluations were performed. The phenotypic characteristics of the patients with molecular changes were examined for genotype-phenotype relations.ResultsPathogenic variants inSNCA,PRKN,DJ-1,FBXO7, andGBAgenes were determined in 25 patients from 24 families (24/79, 30%). Associated variants were found inPRKNin 14,SNCAin three,FBXO7in two, andDJ-1in one patient. A novel homozygous deletion (c.491delT, p.(V164Dfs*13) (SCV001733595)) leading toproteintruncation in thePRKNgene was identified in two patients from the same family. Furthermore, heterozygousGBAgene variants were detected in five patients from different families.ConclusionIt has been shown that the most common cause of genetically transmitted PD is thePRKNgene, whileLRRK2does not play an essential role in this selected population. It has been suggested that even if theautosomal recessive inheritanceis expected, genes withautosomal dominanteffects such asSNCAshould not be overlooked and suggested for investigation. Our study is also the first for evaluating the pathogenicGBAvariants’ frequency in PD patients from Turkey.