Population-specific screening by mutation analysis for diseases frequent in Ashkenazi Jews

Jean M. DeMarchi, C. Thomas Caskey, C. Sue Richards

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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 carders, and 62 were cystic fibrosis carders. 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 carded out efficiently by DNA analysis, with the accrual of carder 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.

Original languageEnglish (US)
Pages (from-to)116-125
Number of pages10
JournalHuman mutation
Issue number2
StatePublished - 1996
Externally publishedYes


  • Allele-specific oligonucleotide
  • Ashkenazi Jewish
  • Cystic fibrosis
  • DNA analysis
  • Gaucher disease
  • PCR
  • Population screening
  • Robotics
  • Tay-Sachs disease

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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