Mutations for Gaucher Disease Confer High Susceptibility to Parkinson Disease

Abstract

Background: Increased frequency of pathogenic variants in GBA, the causative gene for Gaucher disease, has been suggested to be associated with Parkinson disease (PD).Objectives: To conduct comprehensive resequencing of GBA to identify all sequence variants and to investigate the association of these variants with PD.

Multiplexed resequencing analysis to identify rare variants in pooled DNA with barcode indexing using next-generation sequencer

“…2 We and other groups have recently found that multiple rare variants of the glucocerebrosidase gene (GBA) confer a robust risk for Parkinson disease (PD). [3][4][5][6] Our findings have confirmed that multiple rare variants, which can be identified only by extensive resequencing, considerably contribute to the pathogenesis of common diseases such as PD. 5,6 However, even for a particular gene, it is tremendously laborious to detect all the variants in a large number of samples, and efficient methods of detecting multiple rare variants should be established.…”

“…In contrast, the genes identified on the basis of the 'common disease-multiple rare variants' are considered to have large effect sizes. [3][4][5][6] To identify all the rare variants, comprehensive resequence analyses of candidate genes or eventually all the genes in the human genome are required. To accomplish this aim, efficient methods of resequencing genes in a large number of samples should be established.…”

Newborn Screening for Lysosomal Storage Disorders in Hungary

“…Furthermore, seven carriers for Gaucher disease were identified, the mutations c.1226 A>G (p.N409S) (Tsuji et al 1988) and c.1223 C>T (p.T408M) (Beutler et al 1996) occurring once and five times, respectively, and both linked to the type I of Gaucher disease (Amaral et al 2000;Miocić et al 2005;Nichols et al 2009). In addition, both c.1223 C>T (p.T408M) (Beutler et al 1996) and c.475 C>T (p.R159W) (Horowitz and Zimran 1994) have been proven to be connected with Parkinson's disease (Hodanová et al 1999;Amaral et al 2000;Mitsui et al 2009). Overall, clinically relevant phenotypes in Gaucher patients as well as carriers have been identified.…”

Early-onset Parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: Do PGK-1 mutations contribute to vulnerability to Parkinsonism?

“…5 We may have encountered a similar situation in this family. Neurologists and pediatricians should therefore look carefully for parkinsonism in not only PGK-1 deficiency patients but also carriers of this deficiency.…”