Mutation spectrum of α-Galactosidase gene in Japanese patients with Fabry disease.

Abstract

The efficacy of pharmacological chaperone therapy for Fabry disease depends on the type of α-galactosidase A (GLA) mutations. Here, we examined the mutation spectrum of the GLA gene among patients from 115 Japanese families with Fabry disease. Of these, no pathogenic mutations were identified in six families (5.2%). In total, 73 different disease-causing mutations were identified: 41 missense (56.2%), 11 nonsense (15.1%), four in frame deletion (5.5%), 10 frameshift (13.7%), six splice site (8.2%), and one intronic (1.4%) mutations. The GLA mutations detected in later-onset phenotype patients with end-stage renal disease overlapped with those seen in classical patients, indicating that it is difficult to differentiate between these two phenotypes from gene mutations. Additionally, 33 families (28.7%) had amenable mutations to the pharmacological chaperone migalastat. In conclusion, our study is informative when considering genetic counseling and pharmacological chaperon therapy for Fabry disease.

• Authors: Masahisa Kobayashi, Toya Ohashi, Eiko Kaneshiro, Takashi Higuchi, Hiroyuki Ida
• Journal: Journal of human genetics (J Hum Genet) Vol. 64 Issue 7 Pg. 695-699 (Jul 2019) ISSN: 1435-232X [Electronic] England
• PMID: 30988410 (Publication Type: Journal Article)

Chemical References

• 1-Deoxynojirimycin
• migalastat
• alpha-Galactosidase

Topics

• 1-Deoxynojirimycin (analogs & derivatives, therapeutic use)
• Fabry Disease (drug therapy, genetics)
• Female
• Frameshift Mutation
• Humans
• Japan
• Male
• Mutation
• Mutation, Missense
• Sequence Deletion
• alpha-Galactosidase (genetics)