Copy number analysis from whole-exome sequencing data revealed a novel homozygous deletion in PARK7 leads to severe early-onset Parkinson's disease

Mohammad Reza Seyedtaghia; Mohammad Soudyab; Mohammad Shariati; Reza Jafarzadeh Esfehani; Shabnam Vafadar; Neda Shalaei; Vahid Nouri; Michael Zech; Julianne Winkelmann; Ali Shoeibi; Ariane Sadr-Nabavi

doi:10.1016/j.heliyon.2023.e15393

Copy number analysis from whole-exome sequencing data revealed a novel homozygous deletion in PARK7 leads to severe early-onset Parkinson's disease

Heliyon. 2023 Apr 8;9(4):e15393. doi: 10.1016/j.heliyon.2023.e15393. eCollection 2023 Apr.

Authors

Mohammad Reza Seyedtaghia^{1

2}, Mohammad Soudyab^{1

2}, Mohammad Shariati^{3

4}, Reza Jafarzadeh Esfehani², Shabnam Vafadar³, Neda Shalaei³, Vahid Nouri⁴, Michael Zech^{5

6}, Julianne Winkelmann^{5

6

7

8}, Ali Shoeibi³, Ariane Sadr-Nabavi^{1

2

3

4

5

6}

Affiliations

¹ Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
² Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
³ Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁴ Academic Center for Education, Culture, and Research (ACECR)-Khorasan Razavi, Mashhad, Iran.
⁵ Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
⁶ Institut für Humangenetik, Technische Universität München, Munich, Germany.
⁷ Lehrstuhl für Neurogenetik, Technische Universität München, Munich, Germany.
⁸ Munich Cluster for Systems Neurology, SyNergy, Munich, Germany.

Abstract

Parkinson's disease (PD), a neurodegenerative disease characterized by both motor neuron and non-motor neuron symptoms, is the most frequent neurodegenerative disease after Alzheimer's disease. Both genetic and environmental factors take part in disease etiology. Most cases are considered complex multifactorial diseases. About 15% of PD appear in the familial form, and about 5% of all cases arise from a single gene mutation. Among Mendelian causes of PD, PARK7 is one of the autosomal recessive forms due to loss-of-function mutations in both gene alleles. Both single nucleotide variants (SNVs) and copy number variations (CNVs) are observed in PARK7. This study presents an Iranian family with familial PD where some relatives had psychiatric disorders. A homozygous 1617 bp deletion in a female with early-onset PD was detected through copy-number analysis from whole-exome sequencing (WES) data in this consanguineous family. Further investigation by surveying microhomology revealed that the actual size of the deletion is 3,625 bp. This novel CNV that was in the PARK7gene is supposed to co-relation with early-onset PD and infertility in this family.

Keywords: Alu repeats; CNV; PARK7; Parkinson's disease; WES.

Publication types

Case Reports