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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 570-575 |
| Number of pages | 6 |
| Journal | New England Journal of Medicine |
| Volume | 316 |
| Issue number | 10 |
| State | Published - 1987 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Medicine(all)
Cite this
A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease. / Tsuji, S.; Choudary, Prabhakara V; Martin, B. M.; Stubblefield, B. K.; Mayor, J. A.; Barranger, J. A.; Ginns, E. I.
In: New England Journal of Medicine, Vol. 316, No. 10, 1987, p. 570-575.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease
AU - Tsuji, S.
AU - Choudary, Prabhakara V
AU - Martin, B. M.
AU - Stubblefield, B. K.
AU - Mayor, J. A.
AU - Barranger, J. A.
AU - Ginns, E. I.
PY - 1987
Y1 - 1987
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0023131172&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023131172&partnerID=8YFLogxK
M3 - Article
C2 - 2880291
AN - SCOPUS:0023131172
VL - 316
SP - 570
EP - 575
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 10
ER -