This test analyzes the WRN gene, which is associated with Werner syndrome. This rare condition is characterized by short stature, premature onset of features associated with normal aging (with onset usually in the second decade of life), and a predisposition to cancer.
While many of the typical signs and symptoms of Werner syndrome evolve with age, genetic testing by analysis of the WRN gene can confirm a diagnosis. At-risk relatives can be identified, allowing pursuit of a diagnostic evaluation, early detection, and improved clinical outcome.
Werner syndrome is a rare, inherited condition that is characterized by short stature and premature aging, including thinning and graying hair, aged skin, cataracts, diabetes mellitus, osteoporosis, atherosclerosis, and cancer.
Onset of features is typically in the second or third decade of life, with an average age of clinical diagnosis in the late thirties. The most common cause of mortality is cancer, followed by vascular disease such as atherosclerosis.
Cancers associated with Werner syndrome include soft-tissue sarcomas, osteosarcomas, melanomas, and thyroid carcinomas.
Due to the rarity of Werner syndrome, the lifetime risk of developing specific tumors is unknown; however, as affected individuals age, there is an increased risk of developing many different types of cancer, including soft-tissue sarcomas, osteosarcomas, melanomas, and thyroid carcinomas.
Werner syndrome is inherited in an autosomal recessive manner.
The prevalence in the US population is estimated at 1 in 200,000, but founder mutations have been reported in the Japanese and Sardinian populations, leading to an increased prevalence ranging from 1 in 20,000 to 1 in 50,000.
Analysis of the WRN gene may considered in individuals with the following symptoms:
The International Registry of Werner Syndrome provides detailed diagnostic criteria.
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|
WRN: Deletion/duplication analysis is not offered for exons 10 or 11.