The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects.

Abstract

BACKGROUND:

Gaucher 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.

RESULTS:

The 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.

CONCLUSION:

The 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.

• Authors: Yoo-Mi Kim, Jin-Ho Choi, Gu-Hwan Kim, Young Bae Sohn, Jung Min Ko, Beom Hee Lee, Chong Kun Cheon, Han Hyuk Lim, Sun-Hee Heo, Han-Wook Yoo
• Journal: Orphanet journal of rare diseases (Orphanet J Rare Dis) Vol. 15 Issue 1 Pg. 318 (11 11 2020) ISSN: 1750-1172 [Electronic] England
• PMID: 33176831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• GBA protein, human
• Glucosylceramidase

Topics

• Adolescent
• Adult
• Canada
• Child
• Child, Preschool
• Gaucher Disease (genetics)
• Glucosylceramidase (genetics)
• Humans
• Infant
• Middle Aged
• Mutation (genetics)
• Neuroprotective Agents
• Republic of Korea
• Young Adult