Tay-Sachs Disease (HEXA), 7 Variants

Background information for Tay-Sachs Disease (HEXA), 7 Variants:
Characteristics: Tay-Sachs disease is a lysosomal storage disease that, in the most severe childhood-onset form, leads to a loss of motor skills beginning at 3- to 6-months of age and progresses to blindness, seizures, total incapacitation, and eventual death by 4 years of age. Adult-onset Tay-Sachs is a milder disease with later onset and slower progression. In adults, Tay-Sachs disease is associated with variable neurological findings, including progressive dystonia, spinocerebellar degeneration, motor neuron disease, and bipolar form of psychosis.
Incidence: 1 in 3000 Ashkenazi Jewish individuals.
Inheritance: Autosomal recessive.
Cause: HEXA gene pathogenic variants.
Variants Tested: Four pathogenic 7.6kb del, c.1073+1G>A, p.Y427Ifs (c.1274_1277dup TATC), c.1421+1G>C; one mild pathogenic p.G269S (c.805G>A); and two pseudodeficiency alleles p.R247W (c.739C>T) and p.R249W (c.745C>T).
Clinical Sensitivity: 94 percent in Ashkenazi Jewish individuals, 59 percent in other ethnicities.
Methodology: Polymerase chain reaction (PCR) and fluorescence monitoring.
Analytical Sensitivity and Specificity: Greater than 99 percent.
Limitations: HEXA variants other than those specified above will not be detected. Diagnostic errors can occur due to rare sequence variations.

This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.