This test analyzes the RB1 gene for the hereditary form of retinoblastoma (Rb), which is a rare cancer that forms in the retina of the eye. Retinoblastoma typically develops in children under the age of 5. Most cases are sporadic, but approximately 40% are inherited. In addition to Rb, those with the hereditary form of this condition are also at increased risk to develop other non-ocular tumors, including pinealoma, osteosarcoma, soft tissue sarcomas, and melanoma.
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. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Retinoblastoma (Rb) is a rare, early-childhood cancer that forms in the retina of the eye. Most cases are sporadic, unilateral, and diagnosed before the age of 5; however, 40% are bilateral and due to an inherited pathogenic variant in the RB1 gene. Those with hereditary Rb also have an increased risk of developing other cancers outside of the eye, including pinealoma, osteosarcoma, soft tissue sarcomas, and melanoma. These typically present in adolescence and adulthood.
Common early clinical signs of Rb are leukocoria (white pupillary reflex), strabismus, vision loss, persistent eye pain, redness, and irritation. Retinoblastoma is often curable when diagnosed early, but if it is left untreated, this cancer can metastasize and become life-threatening.
Patients with hereditary retinoblastoma carry a significant risk of secondary nonocular tumors. Radiation therapy administered before the age of 12 months is known to increase this risk.
|pinealoblastoma||up to 5.5% (PMID: 23876864)|
|soft tissue sarcomas, osteosarcoma, carcinoma, melanoma, leukemia||elevated (PMID: 22355046)|
Analysis of the RB1 gene identifies a pathogenic variant in more than 95% of individuals with hereditary retinoblastoma.
Rb is inherited in an autosomal dominant manner. A few cases are inherited, but most occur as the result of a spontaneous new mutation.
The prevalence of retinoblastoma is estimated at between 1 in 15,000 and 1 in 20,000 individuals.
Analysis of the RB1 gene may be considered for individuals with:
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|