Tay-Sachs Disease Molecular DNA Assay


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Subject: Tay-Sachs Disease Molecular DNA Assay

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  • Tay-Sachs disease (TSD; OMIM# 272800) molecular DNA testing identifies mutations in the hexosaminidase A gene but should be used concurrently with the hexosaminidase A (HEX A) enzyme activity assay to diagnose TSD. HEX A enzymatic activity is the primary method for diagnosing TSD or carrier identification. HEX A activity is determined by the ratio of HEX A to total hexosaminidase and can be measured in serum from women who are not pregnant and not using oral contraceptives, serum from male patients, or WBCs from individuals.

  • Normal values: negative or no mutations are found.


  • Confirmation of a clinical diagnosis.

  • Carrier testing for Ashkenazi Jewish individuals.

  • Carrier testing for at-risk family members of affected individuals.

  • Confirmation that the reduced HEX A enzymatic activity is caused by a disease-causing allele rather than a pseudodeficiency allele, R247W or R249W. About 35% of non-Jewish individuals and 2–4% of Jewish individuals identified as heterozygotes by HEX A enzyme assay testing are carriers of a pseudodeficiency allele.

  • Prenatal diagnosis: when both parental mutations are known.

  • Identification for genetic counseling of specific disease-causing alleles in affected individuals and carriers.

  • Available tests can be grouped as

    • Targeted mutation analysis

      • A panel of six mutations comprising

        • c.1274_1277dupTATC (+TATC1278), c.1421+1G>C (IVS12+1G>C), p.G269S (Gly269Ser), c.1073+1G>A (IVS9+1G>A)

        • p.R247W (Arg247Trp) and p.R249W (Arg249Trp): the two pseudodeficiency alleles that do not cause TSD but reduce HEX A enzymatic activity as measured by the synthetic substrate

      • More extended panels include ethnic-specific mutations as c.805+1G>A (IVS7+1G>A), del 7.6kb, p.R170Q (Arg170Gln), p.R170W (Arg170Trp), deltaF304/305 (c.915_917delCTT), c.571-2A>G (IVS5-2A>G)

    • HEX A gene sequence analysis: analysis of the entire coding region and exon–intron boundaries useful for identifying rare mutant alleles associated with TSD


  • The results of a genetic test may be affected by DNA rearrangements, blood transfusion, bone marrow transplantation, or rare sequence variations.