AUTHOR=Eis Peggy S. , Huang Neng , Langston J. William , Hatchwell Eli , Schüle Birgitt 

TITLE=Loss-of-Function NUBPL Mutation May Link Parkinson's Disease to Recessive Complex I Deficiency

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.555961

DOI=10.3389/fneur.2020.555961

ISSN=1664-2295

ABSTRACT=<p>In an unbiased genome-wide screen for copy number variants (CNVs) on a cohort of Parkinson's disease (PD) patients, we identified in one patient a complex chromosomal rearrangement involving the nucleotide binding protein-like (<italic>NUBPL</italic>) gene on chromosome 14q12. We noted that mutations in the <italic>NUBPL</italic> gene had been reported as causing autosomal recessive (AR) mitochondrial Complex I (CI) deficiency in children. The precise breakpoints of the rearrangement in our PD case were found to be identical to those described in a patient with AR CI deficiency who also harbored a second pathogenic mutation in <italic>NUBPL</italic>. Mitochondrial dysfunction has long been considered a strong contributor to PD, and there is substantial evidence that decreased CI activity plays a central role in PD pathogenesis. We hypothesize that pathogenic <italic>NUBPL</italic> variants may increase the risk for PD analogous to variants in the glucosylceramidase beta (<italic>GBA</italic>) gene that increase the risk of developing PD in heterozygous carriers.</p>