The Invitae Choroideremia Test analyzes the CHM gene, which is associated with choroideremia, a disorder that is characterized by chorioretinal degeneration. This gene is the only gene currently known to cause choroideremia.
Genetic testing of this gene may confirm a diagnosis and help determine prognosis. Identification of a disease-causing variant can inform recurrence-risk and genetic counseling.
Choroideremia is characterized by progressive loss of vision in males with onset of night blindness in early childhood, followed by loss of peripheral vision and a loss of visual acuity later in life. This loss in vision is caused by progressive chorioretinal degeneration. Carrier females are generally asymptomatic, although some signs of chorioretinal degeneration have been observed. Carrier females may develop night blindness and visual field loss later in life.
Sequencing and duplication/deletion analysis of the CHM gene identifies causative variants in approximately 78% to 95% of individuals with suspected or confirmed choroideremia.
Choroideremia is inherited in an X-linked manner.
Complete penetrance is expected in males. Carrier females are generally asymptomatic, although some signs of chorioretinal degeneration have been observed. Carrier females may develop night blindness and visual field loss later in life.
Choroideremia occurs in an estimated 1 in 50,000 – 100,000 individuals.
Testing may be considered for individuals with a fundus examination consistent with choroideremia.
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|