A candidate loss-of-function variant in SGIP1 causes synaptic dysfunction and recessive parkinsonism.

ABSTRACT: Synaptic dysfunction is recognized as an early step in the pathophysiology of parkinsonism. Several genetic mutations affecting the integrity of synaptic proteins cause or increase the risk of developing disease. We have identified a candidate causative mutation in synaptic "SH3GL2 Interacting Protein 1" (SGIP1), linked to early-onset parkinsonism in a consanguineous Arab family. Additionally, affected siblings display intellectual, cognitive, and behavioral dysfunction. Metabolic network analysis of [¹⁸F]-fluorodeoxyglucose positron emission tomography scans shows patterns very similar to those of idiopathic Parkinson's disease. We show that the identified SGIP1 mutation causes a loss of protein function, and analyses in newly created Drosophila models reveal movement defects,

SUBMITTER: Decet M 

PROVIDER: S-EPMC11513836 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature