Glucocerebrosidase (GBA) gene variants in a multi-ethnic Asian cohort with Parkinson’s disease: mutational spectrum and clinical features

Monogenic Parkinson’s Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing

“…However, this number varies significantly across different ethnic groups, ranging between 2.3% and 12% in populations of non-Ashkenazi Jewish origin to 10–31% in Ashkenazi Jews [ 124 ]. GBA variants were more common in patients with early-onset disease (<50 years), more rapid development of dementia, and a more aggressive motor course [ 125 , 126 ]. Pathogenic variants in this gene have a low, age-dependent penetrance in PD, which is highly variable across different reports, ranging between 8% and 30% by age 80 years [ 127 , 128 , 129 , 130 ].…”

Parkinsonism with a double mutation p.L483P in GBA and p.S231P in LRRK2 following acute hypoxic insult

“…The OR for any GBA mutation in patients with PD was about 5.4 compared with control without PD [10] . The PD carrying pathogenic GBA mutations had about 5 years younger on disease onset, more advanced H&Y score, higher problility to suffer postural instability gait difficulty, but similar respond to levodopa compared with the non-carried [10] . In Chinese Han population, L444P is a most important GBA mutation with increased risk for PD [11] .…”

Rare homozygous PRKN exon 7 duplication in a Ibanese patient from Northwestern Borneo with young onset Parkinson’s disease

“…20 However, truncal dystonia may not be specific to PRKN, since this feature has also recently been observed, for example, in PD cases associated with Glucocerebrosidase (GBA) gene mutations. 10 The collection and analysis of large genotypephenotype datasets (for example, as part of the ongoing Global Parkinson's Genetics Project or GP2; https://gp2.org) will provide clarity on the potential for this, as well as other features, to be useful differentiating signs in clinical practice.…”

“…1,[5][6][7][8] This deficit is even more pronounced among the indigenous populations of Southeast Asia. 9,10 Island Southeast Asia (ISEA), including the island of Borneo, is home to hundreds of different ethnic groups, with rich cultural, linguistic, and genetic diversities. 11,12 Although previous studies have suggested a common origin of all Southeast Asian populations through a single north-to-south migration wave, more recent research revealed a multi-layered population structure in the ISEA, with at least three major ancestral components in association with Papuan-, Austroasiatic-and Austronesian-speaking populations.…”