Paired Copy Number Variation Analysis in Siblings Discordant for Familial Parkinson's Disease.

IF 2.1 4区医学 Q3 MEDICAL LABORATORY TECHNOLOGY Annals of Clinical Biochemistry Pub Date : 2025-03-04 DOI:10.1177/00045632251328130

Sevcan Atay, Ahmet Acarer, Handan Ak, Zafer Colakoglu, Hikmet Hakan Aydin

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Abstract

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 variation was detected in 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 PH risk genes. The metabolism of xenobiotics by cytochrome P450 pathway deserves further functional and translational studies in familial Parkinson's disease.

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来源期刊

Annals of Clinical Biochemistry Biochemistry, Genetics and Molecular Biology-Clinical Biochemistry

CiteScore

5.20

自引率

4.50%

发文量

期刊介绍： Annals of Clinical Biochemistry is the fully peer reviewed international journal of the Association for Clinical Biochemistry and Laboratory Medicine. Annals of Clinical Biochemistry accepts papers that contribute to knowledge in all fields of laboratory medicine, especially those pertaining to the understanding, diagnosis and treatment of human disease. It publishes papers on clinical biochemistry, clinical audit, metabolic medicine, immunology, genetics, biotechnology, haematology, microbiology, computing and management where they have both biochemical and clinical relevance. Papers describing evaluation or implementation of commercial reagent kits or the performance of new analysers require substantial original information. Unless of exceptional interest and novelty, studies dealing with the redox status in various diseases are not generally considered within the journal''s scope. Studies documenting the association of single nucleotide polymorphisms (SNPs) with particular phenotypes will not normally be considered, given the greater strength of genome wide association studies (GWAS). Research undertaken in non-human animals will not be considered for publication in the Annals. Annals of Clinical Biochemistry is also the official journal of NVKC (de Nederlandse Vereniging voor Klinische Chemie) and JSCC (Japan Society of Clinical Chemistry).