Genetic heterogeneity in type 1 Gaucher disease: multiple genotypes in Ashkenazic and non-Ashkenazic individuals.

• S Tsuji

  Molecular Neurogenetics Unit, National Institute of Mental Health, ADAMHA, Bethesda, MD 20892.

• B M Martin

  Molecular Neurogenetics Unit, National Institute of Mental Health, ADAMHA, Bethesda, MD 20892.

• J A Barranger

  Molecular Neurogenetics Unit, National Institute of Mental Health, ADAMHA, Bethesda, MD 20892.

• B K Stubblefield

  Molecular Neurogenetics Unit, National Institute of Mental Health, ADAMHA, Bethesda, MD 20892.

• M E LaMarca

  Molecular Neurogenetics Unit, National Institute of Mental Health, ADAMHA, Bethesda, MD 20892.

• E I Ginns

  Molecular Neurogenetics Unit, National Institute of Mental Health, ADAMHA, Bethesda, MD 20892.

Abstract

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in the type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is approximately equal to 80% informative in all Gaucher patients studied.

Journal

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 85 (7), 2349-2352, 1988-04

  Proceedings of the National Academy of Sciences

Keywords

• Multidisciplinary

Details

• CRID: 1362825896128306048
• NII Article ID: 30016284603
• DOI: 10.1073/pnas.85.7.2349
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.85.7.2349
• Data Source:
  • Crossref
  • CiNii Articles