Gaucher's disease: identification of novel mutant alleles and genotype-phenotype relationships

Clin Genet. 2003 Jul;64(1):57-64. doi: 10.1034/j.1399-0004.2003.00100.x.


A sequencing protocol for the acid beta-glucosidase (GCase) gene (GBA) was developed using a long-range PCR template. This protocol has an advantage of greater DNA yields over similar strategies. Seven Gaucher's disease patients had four novel and five other rare alleles. A non-pseudogene in-frame deletion (g.2600-2602delTAC) and a new complex mutation (null allele) were identified in Gaucher's disease type 1, i.e. the g.2600-2602delTAC deletion is associated with the non-neuronopathic variant. An F251L allele was found in a baby with the collodion skin phenotype. Three mutant alleles were identified in a single primary family with type 3. The patients' father at 45 years is healthy and is heteroallelic for the G202R and E326K alleles. Family studies indicated that E326K is in trans to G202R and L444P, and that isolated E326K is non-pathogenic in this family. A rare mutation R257Q was identified in a type 2 patient, providing an association with neuronopathic disease. A genotype L444P/L444P was noted in a 22-year-old non-neuronopathic patient. Complete gene sequencing showed a new complex allele consisting of L444P and g.7741T > C in the 3' UTR. Three additional complex alleles also involved the 3' UTR. Complete gene characterization in Gaucher's disease should allow greater insights into the correlation of specific alleles with phenotype.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • DNA Mutational Analysis
  • Female
  • Gaucher Disease / enzymology
  • Gaucher Disease / genetics*
  • Genotype
  • Glucosylceramidase / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation
  • Pedigree
  • Phenotype


  • Glucosylceramidase