The Invitae Canavan Disease Test analyzes ASPA, the gene that is associated with Canavan disease, a rare leukodystrophy. Genetic testing of the ASPA gene may confirm a diagnosis and help guide treatment and management decisions.
Canavan disease is a rare neurodegenerative disorder that is characterized by the degeneration of the myelin sheath that insulates nerve cells (leukodystrophy). The loss of myelin leads to progressive neurological damage. The most common form of Canavan disease starts in infancy, with infants appearing normal for the first few months of life and then, by age 3–5 months, presenting with macrocephaly, hypotonia, and developmental delay. There is a less-common and more mild form of this disorder, in which symptoms first present in late childhood or early adolescence.
Patients with Canavan disease typically have increased levels of N-acetylaspartic acid (NAA) in urine; however, patients with the milder form of the disease may not always have increased urine NAA. Therefore, molecular testing should be considered in patients with clinical suspicion of Canavan disease, despite negative urine results.
Pathogenic variants are found in more than 98% of Ashkenazi Jews and more than 87% in non-Ashkenazi Jewish individuals.
Canavan disease is inherited in an autosomal recessive manner.
Canavan disease is more common among Ashkenazi Jews. Carrier frequency in Ashkenazi Jews is 1 in 57–82. Carrier frequency in the general population is thought to be much lower.
Infants with evidence of white matter disease or elevated NAA in blood, cerebrospinal fluid, and urine should have molecular confirmation of Canavan disease. For juvenile or mild cases, neuroimaging may not be suggestive and urine NAA may only be slightly elevated.
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|