AUTHOR=Vieira Sophia R. L. , Morris Huw R. 

TITLE=Neurodegenerative Disease Risk in Carriers of Autosomal Recessive Disease

JOURNAL=Frontiers in Neurology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.679927

DOI=10.3389/fneur.2021.679927

ISSN=1664-2295

ABSTRACT=<p>Genetics has driven significant discoveries in the field of neurodegenerative diseases (NDDs). An emerging theme in neurodegeneration warrants an urgent and comprehensive update: that carrier status of early-onset autosomal recessive (AR) disease, typically considered benign, is associated with an increased risk of a spectrum of late-onset NDDs. <italic>Glucosylceramidase beta</italic> (<italic>GBA1</italic>) gene mutations, responsible for the AR lysosomal storage disorder Gaucher disease, are a prominent example of this principle, having been identified as an important genetic risk factor for Parkinson disease. Genetic analyses have revealed further examples, notably <italic>GRN, TREM2, EIF2AK3</italic>, and several other LSD and mitochondria function genes. In this Review, we discuss the evidence supporting the strikingly distinct allele-dependent clinical phenotypes observed in carriers of such gene mutations and its impact on the wider field of neurodegeneration.</p>