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Population‐specific screening by mutation analysis for diseases frequent in Ashkenazi Jews
Author(s) -
DeMarchi Jean M.,
Caskey C. Thomas,
Richards C. Sue
Publication year - 1996
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1996)8:2<116::aid-humu3>3.0.co;2-9
Subject(s) - tay sachs disease , biology , population , mutation , cystic fibrosis transmembrane conductance regulator , cystic fibrosis , disease , genotype , genetics , microbiology and biotechnology , gene , medicine , environmental health
We describe a partially automated DNA mutation assay for detecting the most frequent mutations in the α‐subunit of β‐hexosaminidase A, the acid β‐glucosidase and the cystic fibrosis transmembrane conductance regulator genes for the Ashkenazi Jewish population. The assay detects carriers for Tay‐Sachs disease, Gaucher disease, and cystic fibrosis with sensitivities of at least 92%, 96%, and 97%, respectively. Among 1,364 young adults of Ashkenazic ancestry in the Dor Yeshurim community who were tested, 52 were Tay‐Sachs carriers, 110 were Gaucher carriers, and 62 were cystic fibrosis carriers. Ten individuals were carriers for two diseases, and three unsuspected cases were diagnosed with Gaucher disease based on mutation test results. In addition to Tay‐Sachs mutation data, results for hexosaminidase A activity were also available. All of 1,254 samples normal by enzyme quantitation were also negative for the three α‐subunit mutations tested, and all of 43 samples with ‘inconclusive’ enzyme results were negative by DNA. Only 52 of 67 samples positive by enzyme assay were also positive for one of the three mutations tested for Tay‐Sachs disease. The data suggest a high degree of false positivity inherent in enzyme identification of carriers. There are no correlative methods to assess the sensitivity of Gaucher and CF carrier testing. The results show that population screening can be carried out efficiently by DNA analysis, with the accrual of carrier information for three separate diseases conducted as a single test. Furthermore, the DNA method for Tay‐Sachs screening appears to exceed the specificity of hexosaminidase A enzyme testing. © 1996 Wiley‐Liss, Inc.