Co-occurrence of PRKN and SYNJ1 Variants in Early-Onset Parkinson's Disease

Overview

Journal Metab Brain Dis

Publisher Springer

Specialties Endocrinology
Neurology

Date 2024 Jun 5

PMID 38836947

Authors

Juliana Cordovil Cotrin

Rafael Mina Piergiorge

Andressa Pereira Goncalves

Joao Santos Pereira

Alexandra Lehmkuhl Gerber

Ana Paula de Campos Guimaraes

Ana Tereza Ribeiro de Vasconcelos

Cintia Barros Santos-Reboucas

Affiliations

Soon will be listed here.

Abstract

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease globally, with a fast-growing prevalence. The etiology of PD exhibits a multifactorial complex nature and remains challenging. Herein, we described clinical, molecular, and integrative bioinformatics findings from a Brazilian female affected by Early-Onset PD (EOPD) harboring a recurrent homozygous pathogenic deletion in the parkin RBR E3 ubiquitin protein ligase gene (PRKN; NM_004562.3:c.155delA; p.Asn52Metfs*29; rs754809877), along with a novel heterozygous variant in the synaptojanin 1 gene (SYNJ1; NM_003895.3:c.62G > T; p.Cys21Phe; rs1486511197) found by Whole Exome Sequencing. Uncommon or unreported PRKN-related clinical features in the patient include cognitive decline, auditory and visual hallucinations, REM sleep disorder, and depression, previously observed in SYNJ1-related conditions. Moreover, PRKN interacts with endophilin A1, which is a major binding partner of SYNJ1. This protein plays a pivotal role in regulating the dynamics of synaptic vesicles, particularly in the context of endocytosis and recycling processes. Altogether, our comprehensive analyses underscore a potential synergistic effect between the PRKN and SYNJ1 variants over the pathogenesis of EOPD.

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