Tay-Sachs Disease (HEXA) Sequencing and 7.6kb Deletion

Background for Tay-Sachs Disease (HEXA) Sequencing and 7.6kb Deletion:
Characteristics:  Hexosaminidase A (HEX A) enzyme deficiency is characterized by neuronal deterioration resulting in intellectual disability and motor retardation. Clinical severity is variable.  Onset by six months of age with rapid progression is seen with Tay-Sachs disease (acute infantile form), while juvenile and adult-onset forms manifest a less severe course. HEX A deficiency results in the accumulation and lysosomal storage of GM2 (ganglioside).
Incidence: Varies by ethnicity. 1 in 3,000 for Ashkenazi Jewish and French Canadians; other high-risk populations include Louisiana Cajuns and Old Order Amish. 1 in 300,000 for the general population.
Inheritance: Autosomal recessive.
Cause: Two pathogenic germline HEXA gene mutations on opposite chromosomes.
Clinical Sensitivity: 99 percent.
Methodology: Bidirectional sequencing of all coding regions and intron/exon boundaries of the HEXA gene. Agarose gel electrophoresis to assess for the 7.6kb deletion.
Analytical Sensitivity and Specificity: 99 percent.
Limitations:  Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations and deep intronic mutations will not be detected. Large deletions/duplications in HEXA, other than the 7.6kb deletion, will not be detected.