Premium
Neurological effects of glucocerebrosidase gene mutations
Author(s) -
Mullin S.,
Hughes D.,
Mehta A.,
Schapira A. H. V.
Publication year - 2019
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13837
Subject(s) - glucocerebrosidase , medicine , allele , disease , phenotype , genetics , mutation , compound heterozygosity , gene , sphingolipid , pathology , biology
The association between Gaucher disease ( GD ) and Parkinson disease ( PD ) has been described for almost two decades. In the biallelic state (homozygous or compound heterozygous) mutations in the glucocerebrosidase gene ( GBA ) may cause GD , in which glucosylceramide, the sphingolipid substrate of the glucocerebrosidase enzyme ( GC ase), accumulates in visceral organs leading to a number of clinical phenotypes. In the biallelic or heterozygous state, GBA mutations increase the risk for PD . Mutations of the GBA allele are the most significant genetic risk factor for idiopathic PD , found in 5%–20% of idiopathic PD cases depending on ethnicity. The neurological consequences of GBA mutations are reviewed and the proposition that GBA mutations result in a disparate but connected range of clinically and pathologically related neurological features is discussed. The literature relating to the clinical, biochemical and genetic basis of GBA PD , type 1 GD and neuronopathic GD is considered highlighting commonalities and distinctions between them. The evidence for a unifying disease mechanism is considered.