Revisiting the diagnosis of Gaucher disease in a family with multiple GBA1 variants

Am J Med Genet A. 2023 Oct;191(10):2647-2650. doi: 10.1002/ajmg.a.63345. Epub 2023 Jul 14.

Abstract

Our ability to identify different variants in GBA1, the gene mutated in the lysosomal storage disorder Gaucher disease (GD), has greatly improved. We describe a multigenerational family with type 1 GD initially evaluated over three decades ago. Re-evaluating both the genotype and phenotype, we determined that one family member with genotype N370S/T369M (p.N409S/p.T408M), was likely erroneously diagnosed with GD. This case substantiates that GBA1 variant T369M, while mildly reducing glucocerebrosidase activity, does not result in GD. The observation has clinical relevance as cases with this genotype will increasingly be ascertained through screening programs in newborns and in movement disorder clinics.

Keywords: GBA1; Gaucher disease; T369M; genotyping.

Publication types

  • Case Reports
  • Research Support, N.I.H., Intramural

MeSH terms

  • Family
  • Gaucher Disease* / diagnosis
  • Gaucher Disease* / genetics
  • Genotype
  • Glucosylceramidase / genetics
  • Humans
  • Infant, Newborn
  • Mutation
  • Phenotype

Substances

  • Glucosylceramidase