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

Journal Article · Thu Mar 31 23:00:00 EST 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.7.2349· OSTI ID:6810199

Tsuji, Shoji; Martin, B M; Stubblefield, B K; LaMarca, M E; Ginns, E I ^[1]; Barranger, J A ^[2]

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1. National Institute of Mental Health, Bethesda, MD (USA)
2. Childrens Hospital of Los Angeles, CA (USA)

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 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 {approx}80% informative in all Gaucher patients studied.

• OSTI ID: 6810199
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:7; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550401* -- Genetics-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMIDES
AMINO ACIDS
ANIMAL CELLS
ASPARAGINE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
CARBOXYLIC ACIDS
CHEMISTRY
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DIAGNOSIS
DISEASES
DNA
DNA HYBRIDIZATION
ENZYME ACTIVITY
ENZYMES
FIBROBLASTS
GENE MUTATIONS
HEREDITARY DISEASES
HUMAN POPULATIONS
HYBRIDIZATION
HYDROLASES
HYDROXY ACIDS
ISOTOPES
LIGHT NUCLEI
METABOLIC DISEASES
MUTAGENESIS
MUTATIONS
NERVOUS SYSTEM DISEASES
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
OLIGONUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATIENTS
PEPTIDE HYDROLASES
PHENOTYPE
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
POPULATIONS
RADIOISOTOPES
RFLPS
SERINE
SOMATIC CELLS