The Invitae Rubinstein-Taybi syndrome test analyzes CREBBP, a gene associated with Rubinstein-Taybi syndrome (RSTS), a multisystem disorder characterized by short stature, recognizable facial features, broad thumbs and great toes, and moderate to severe intellectual disability.
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.
Rubinstein-Taybi syndrome is characterized by distinctive facial features, broad thumbs, broad great toes, short stature, and intellectual disability. Other associated features include postnatal growth deficiency, obesity in later childhood/adolescence, ophthalmologic anomalies, congenital heart defects, genitourinary anomalies including cryptorchidism in males, and keloid formation. An increased tumor risk has been recognized in Rubinstein-Taybi syndrome.
Approximately 50-60% of patients with a strong clinical suspicion of RSTS have a pathogenic variant in CREBBP.
Rubinstein-Taybi syndrome is inherited in an autosomal dominant manner. Many cases occur de novo, although parent-to-child transmissions and somatic mosaicism have been reported.
Pathogenic variants in CREBBP demonstrate complete penetrance with variable expressivity.
Rubinstein-Taybi syndrome has a prevalence of approximately 1 in 100,000 to 125,000.
This test could be considered for patients who present with intellectual disability, obesity, short stature, broad thumbs and toes, and characteristic facial features including downslanting palpebral fissures, arched brows and grimacing smile. Other clinical features include congenital heart defects, renal abnormalities, cryptorchidism and eye abnormalities.
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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|