title: A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease.
abstract: To search for a genetic marker for type 2 Gaucher's disease (acute neuronopathic form), we compared the nucleotide sequence of a cloned glucocerebrosidase gene from a patient with Gaucher's disease with a normal gene. We found only a single base substitution (T----C) in exon X. This mutation results in the substitution of proline for leucine in position number 444 and produces a new cleavage site for the NciI restriction endonuclease. We analyzed NciI enzymatic digests of genomic DNA from 20 patients with type 1, 5 with type 2, and 11 with type 3 Gaucher's disease, and 29 normal controls for a restriction-fragment-length polymorphism (RFLP). Four of 5 patients with type 2 disease and all 11 with type 3 disease had at least one allele with the mutation. Two of 5 patients with type 2 disease and 7 of 11 with type 3 were homozygous for this mutation. Only 4 of 20 patients with type 1 Gaucher's disease had the mutant allele and were heterozygous for it. None of the 29 normal controls had the mutant allele. The high frequency of this mutation (444leucine----proline) in patients with neuronopathic Gaucher's disease, detectable by the NciI RFLP, may be of value in the identification of patients who will have the neurologic sequelae of Gaucher's disease.
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002648:Child; D005091:Exons; D005776:Gaucher Disease / Q000235:genetics*; D005959:Glucosidases / Q000235:genetics*; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D005959:Glucosidases; D005962:Glucosylceramidase