Abstract
BackgroundGaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients.ResultsThe study cohort included 62 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harbored the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (9%). The median age at diagnosis of the 18 patients harboring the p.G85E mutation was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3075 years.ConclusionThe GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.
Highlights
Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA
This study aimed to investigate the clinical characteristics of GD patients carrying p.G85E mutation and mutation spectrum of GBA among Korean GD patients and to test for a founder effect for the GBA p.G85E mutation via haplotype analysis
Thirty-one patients from 30 families had neuronopathic GD, including 10 with type 2 (16%) and 21 with type 3 (34%) GD
Summary
Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Gaucher disease (GD [MIM: 230,800, 230,900, and 231,000]) is caused by the deficiency of β-glucocerebrosidase (GBA), encoded by GBA [1]. Parkinsonism is not considered as a feature of neuronopathic GD; rather, GBA mutations are one of the risk factors of Parkinsonism [3]. According to the International Collaborative Gaucher Group’s Gaucher Registry (clinicaltrials.gov NCT00358943), ~ 94% of patients in Western countries are of the non-neuronopathic type, whereas half of the patients in Japan, Korea, and China are classified as the neuronopathic type [4].
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