Paired copy number variation analysis in siblings discordant for familial Parkinson’s disease

İngilizce (OpenAlex)

Objectives Numerous studies on the genetic pathogenesis of familial Parkinson’s Disease (PD) have explained the etiology of only a limited percentage of cases. In this study, we aimed to identify copy number variations (CNVs) in patients with familial PD compared to their healthy siblings. Methods Genomic microarray analysis was performed using the CytoScan HD array platform, and paired copy number variation analysis was performed using Partek Genomics Suite. Results A total of 211 CNVs were detected in patients (genomic markers per CNV >10, markers per base pair >0.0005). Genes localized in CNV regions were enriched in the “ Metabolism of xenobiotics by cytochrome P450 ” pathway. Subsequently, CNVs located in regions with segmental duplication, large genomic gap or “dosage sensitivity unlikely,” with a frequency higher than 0.01%, and found to be “both amplified and deleted” in patients were excluded. Genes potentially affected by exonic copy number losses were HPGDS, TUBB8, ZMYND11, FLI-1, THADA, FAM47E, FAM47E-STBD1, AGMO, CYRIB, and MIR5194, while the detected copy number gains included the exons of the PCSK6, MIR4522, WSB1, C8orf44-SGK3, SGK3, and MCMDC2. No copy number variations were detected on chromosomes 13 and 18. Conclusions Here, we report the results of the first paired CNV analysis in siblings discordant for Familial Parkinson’s Disease. Validation and frequency determination of rare and novel CNVs identified in larger familial PD cohorts may reveal novel PD risk genes. The metabolism of xenobiotics by cytochrome P450 pathway deserves further functional and translational studies in familial Parkinson’s disease.