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  • Test code: 06178
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Sandhoff Disease Test

Test description

The Invitae Sandhoff Disease Test analyzes the hexosaminidase B (HEXB) gene. Pathogenic variants in HEXB are known to cause Sandhoff disease. Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.

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Primary panel (1 gene)
Add-on Tay-Sachs Disease Gene (1 gene)

Given the significant clinical overlap between Sandhoff disease and Tay Sachs disease, analyzing HEXA, the gene associated with Tay Sachs, may be appropriate. The HEXA gene can be included at no additional charge.

HEXA

  • Sandhoff disease

Sandhoff disease is a rare progressive neurodegenerative lysosomal disorder in which lipid-containing cells accumulate, affecting the body and central nervous system. It is clinically indistinguishable from Tay Sachs disease. The infantile form is the most severe and most common, with onset typically between three and six months of age. Infants develop seizures and lose developmental milestones, vision, and hearing. A characteristic cherry-red spot is seen on ophthalmologic examination. Organomegaly may be observed. The infantile form of this disorder is fatal, with death usually before four years of age.

Juvenile and adult onset cases of Sandhoff are less common, more mild in presentation, and more slowly progressive. Presentation in older individuals may include ataxia, cognitive impairment, and mental illness; cherry-red spots may not be present. Lifespan for older affected individuals may not be affected.

The HEXB gene encodes the beta subunit of beta-hexosaminidase, which is needed for the formation of both hexosaminidase A (HEXA) and hexosaminidase B (HEXB) enzymes. These enzymes are needed for the breakdown of GM2 ganglioside. Accumulation of GM2 is toxic to cells in the body and central nervous system.

Patients with Sandhoff disease will have low total hexosaminidase activity (both hexosaminidase A and hexosaminidase B). Genetic testing is indicated to confirm the diagnosis, to determine carrier status, and to provide prenatal diagnosis.

For patients with a clinical and biochemical diagnosis of Sandhoff disease, approximately 96% will have two pathogenic variants detected in HEXB.

Pathogenic variants in the HEXB gene are inherited in an autosomal recessive manner.

Incidence in the general population is 1 in 300,000. Several population isolates in northern Argentina, Saskatchewan, and Cyprus have been identified with higher prevalence.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
HEXA NM_000520.4
HEXB NM_000521.3