A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease

S. Tsuji, Prabhakara V Choudary, B. M. Martin, B. K. Stubblefield, J. A. Mayor, J. A. Barranger, E. I. Ginns

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227 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)570-575
Number of pages6
JournalNew England Journal of Medicine
Issue number10
StatePublished - 1987
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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