DNA mutation analysis of Gaucher patients

Authors

  • M.D. Ellen Sidransky,

    Corresponding author
    1. Section on Molecular Genetics, Clinical Neuroscience Branch, National Institute of Mental Health, Building 10, Room 3D16, Bethesda, Maryland
    • Clinical Neuroscience Branch, NIMH, Building 10, Room 3D16, Bethesda, MD, 20892
    Search for more papers by this author
  • Shoji Tsuji,

    1. Section on Molecular Genetics, Clinical Neuroscience Branch, National Institute of Mental Health, Building 10, Room 3D16, Bethesda, Maryland
    Search for more papers by this author
  • Brian M. Martin,

    1. Section on Molecular Genetics, Clinical Neuroscience Branch, National Institute of Mental Health, Building 10, Room 3D16, Bethesda, Maryland
    Search for more papers by this author
  • Barbara Stubblefield,

    1. Section on Molecular Genetics, Clinical Neuroscience Branch, National Institute of Mental Health, Building 10, Room 3D16, Bethesda, Maryland
    Search for more papers by this author
  • Edward I. Ginns

    1. Section on Molecular Genetics, Clinical Neuroscience Branch, National Institute of Mental Health, Building 10, Room 3D16, Bethesda, Maryland
    Search for more papers by this author

Abstract

We evaluated 62 Gaucher patients to determine whether patients with similar phenotypes had the same DNA point mutations. Genomic DNA from these Gaucher patients was screened for the 3 most frequent single-point mutations, occurring in 69% of the 124 patient alleles, and resulting in changes in amino acids 370, 444, and 463. Many different genotypes were observed, at least one of which is present in all 3 types of Gaucher disease. No specific symptom complex could be correlated with a unique genotype. Even the more clinically homogeneous subgroups of Gaucher patients contained several genotypes. This study further emphasizes the need for caution in making clinical predictions on the basis of current genotype analysis, especially since one might not discern a fetus affected with type 2 disease by current DNA studies. The severity of involvement in type 1 disease could also not be predicted. Thus, even limiting our focus to 3 isolated common point mutations, a given genotype cannot be uniquely correlated with a specific prognosis.

Ancillary