Implications of results of HEXA genetic testing

Implications of results of HEXA genetic testing

HEXA genotype	Hexosaminidase A enzyme assay	Clinical phenotype	Management
Heterozygous for a PV or LPV	Approximately half-normal	Unaffected carrier	Preconception counseling Notify at-risk first-degree relatives
Homozygous or compound heterozygous for a PV or LPV	Absent or nearly absent	Tay-Sachs disease	Supportive care to reduce disease morbidities Genetic counseling for parents Notify at-risk first-degree relatives
Compound heterozygous for a PV or LPV plus a pseudodeficiency variant	Absent or nearly absent	Unaffected carrier	Preconception counseling Notify at-risk first-degree relatives
Heterozygous for a pseudodeficiency variant	Approximately half-normal	None	Notify at-risk first-degree relatives

HEXA encodes the alpha subunit of the enzyme hexoaminidase A, which is defective in Tay-Sachs disease (TSD). Pathogenic and likely pathogenic variants (PV and LPV) in HEXA are treated similarly for the purposes of preconception counseling and management. Pseudodeficiency variants, of which two have been well-characterized, reduce enzyme activity in a standard laboratory assay but do not affect enzyme activity in vivo and do not confer increased risk (or carrier status) for TSD. A variant of uncertain significance (VUS) can have its pathogenicity evaluated by an enzyme assay; although this cannot distinguish pseudodeficiency from true deficiency, it is likely that the majority of pseudodeficiency variants have already been characterized. At-risk first-degree relatives include children, parents, and siblings who share genetic material with the tested individual. Refer to UpToDate for additional details.

PV: pathogenic variant; LPV: likely pathogenic variant.

Graphic 129254 Version 3.0

خرید پکیج

Implications of results of HEXA genetic testing