The Invitae Treacher Collins Syndrome test analyzes the TCOF1 gene, which is associated with Treacher Collins syndrome, a condition that is characterized by hypoplasia of the facial bones—particularly the cheek and jaw bones—as well as ear abnormalities and coloboma. Genetic testing of this gene may confirm a diagnosis and help guide treatment and management. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.
Approximately 70%–93% of individuals who meet diagnostic criteria for Treacher Collins syndrome have an identifiable pathogenic variant in TCOF1.
Treacher Collins syndrome is inherited in an autosomal dominant pattern. Approximately 60% of cases are attributable to de novo pathogenic variants.
TCOF1 mutations are highly penetrant; however, cases of reduced penetrance have been reported. Significant inter- and intrafamilial variability has been observed.
The prevalence of Treacher Collins syndrome is approximately 1 in 10,000–50,000.
This test could be considered for patients who present with midface hypoplasia, absent or small, malformed or rotated ears, coloboma, sparse or absent eyelashes, or conductive hearing loss. Other, less-common features include cleft palate with or without cleft lip and choanal stenosis or atresia.
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|