Molecular characterization of type 3 (neuronopathic) Gaucher disease in Thai patients

Blood Cells Mol Dis. 2007 Nov-Dec;39(3):348-52. doi: 10.1016/j.bcmd.2007.06.015. Epub 2007 Aug 8.

Abstract

Gaucher disease is an autosomal recessive lysosomal storage disorder due to deficiency of the lysosomal enzyme glucocerebrosidase. Three clinical phenotypes, type 1, nonneuronopathic; and types 2 and 3, acute and subacute neuronopathic are recognized. The incidence of Gaucher disease in the Thai population is unknown, but likely under-diagnosed. We performed molecular analysis in four patients, from three sibships, with type 3 Gaucher disease. Four mutant glucocerebrosidase (GBA) alleles were identified including two novel splice site mutations, IVS6-1G>C and IVS9-3C>G; both are predicted to result in truncated protein products, p.F255fsX256, and p.K464fsX487 and p.S463fsX480, respectively. One patient, homozygous for the L444P point mutation, had a "Norbottnian-like" phenotype, with more severe visceral involvement, kyphosis, barreled chest, and no neurological involvement other than supranuclear gaze palsy. These molecular studies of neuronopathic Gaucher disease will provide additional genotype-phenotype correlation particularly in non-Caucasian population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Child, Preschool
  • Female
  • Gaucher Disease / enzymology
  • Gaucher Disease / genetics*
  • Gaucher Disease / metabolism
  • Genotype
  • Glucosylceramidase / chemistry
  • Glucosylceramidase / genetics*
  • Glucosylceramidase / metabolism
  • Humans
  • Infant
  • Male
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Point Mutation
  • Sequence Analysis, DNA
  • Thailand

Substances

  • Glucosylceramidase