Glucocerebrosidase mutations in Thai patients with Parkinson's disease

Mitochondrial Respiratory Chain Enzymatic Activities on Skin Fibroblasts in Patients With Mutant Glucocerebrosidase and PARK2 Genes

“…Details of the identification of GBA variants have been described in our previous publication, which can distinguish functional GBA from its pseudogene [17]. To our knowledge, all but p. IVS2+1g>A mutations of the GBA were identified in only Thai PD patients [17]. The PARK2 point mutation, p.M1T, is a novel mutation identified in 0.8% of the Thai PD cohort (4/513), and absent in over 400 control subjects.…”

“…Four patients carried heterozygous GBA point mutations, two had heterozygous deletion of exon 8 of PARK2, one had a heterozygous PARK2 point mutation, and seven remaining patients had no mutations in the genes studied ( Table 1). Details of the identification of GBA variants have been described in our previous publication, which can distinguish functional GBA from its pseudogene [17]. To our knowledge, all but p. IVS2+1g>A mutations of the GBA were identified in only Thai PD patients [17].…”

“…The authors had recent works on a comprehensive genetic analysis of GBA [17] and PARK2 genes (unpublished data), and screening for p.R1628P, p.G2019S and p.G2385R variants of the leucine-rich repeat kinase 2 gene (LRRK2) in a large Thai PD cohort [18]. Here, we recruited the PD patients from the previous cohort for further studying on a mitochondrial respiratory chain function associated with a heterozygous allele of GBA and PARK2 mutations.…”

Dopamine and Early Onset Parkinson’s Disease

“…The study of Sato et al [89] indicates that GBA mutation carriers have a positive history of PD in families. They present poorer motor progression, more often postural instability, persistent asymmetry, and responsive for L-dopa for more than 5 years [91]. According to the literature data, GBA mutations are associated with cognitive impairment, which is revealed by a lower MMSEscore [92].ItisconsideredthatpatientswithbothGDandPDpresentmildGaucher's symptoms [65].…”

Progress and potential of non-inhibitory small molecule chaperones for the treatment of Gaucher disease and its implications for Parkinson disease

“…This was followed by reports of an increased incidence of PD in first degree relatives of patients with GD carrying GBA1 mutations, as well as an increased frequency of GBA1 mutations in small cohorts of patients with PD or related synucleinopathies (Goker-Alpan et al, 2004, Lwin et al, 2004, Eblan et al, 2006, Ziegler et al, 2007). Subsequently, large pan-ethnic cohort studies confirmed a strong association between mutations in GBA1 and the development of synucleinopathies such as PD (26–29), dementia with Lewy bodies (DLB) (30), and multiple system atrophy (MSA) (31). Although GBA1 mutations are now the most common genetic risk factor for the development of PD, only a small percentage of GD patients and GBA1 carriers will go on to develop synucleinopathies.…”