Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Clinical Features
Rubinstein-Taybi syndrome (RTS) (OMIM #180849) is an autosomal dominant disorder characterized by broad thumbs and toes, distinctive facial features, postnatal growth delay, congenital heart defects and moderate to severe intellectual disability. Disease-causing alterations in both CREBBP and EP300 are currently the only genes known to be involved in RTS and the vast majority of variants are de novo. Menke-Hennekam syndrome (OMIM #618332) is an allelic phenotype associated with CREBBP and EP300, typically caused by missense variants in exons 30-31 of CRBBP or the homologous regions of EP300 [GeneReviews 2019, PMID: 20301699].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
Sequencing and copy number analysis of the genes on this panel is estimated to identify 50-60% of alterations associated with the CREBBP gene and 3-8% of alterations associated with the EP300 gene. It is estimated that about 10% of patients with RTS have microdeletions of chromosome 16p13.3 [GeneReviews 2019, PMID: 20301699].
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, and assess the risk to other first-degree relatives and to facilitate testing of at-risk family members. Molecular confirmation of a diagnosis may help guide recommendations for medical management and screening, and may help avoid unnecessary procedures.
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis is based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
CREBBP (CREB binding protein) on chromosome 16p13.3 and EP300 (E1A binding protein p300) on chromosome 22q13.2 are the only genes currently known to be associated with RTS. RTS is inherited in an autosomal dominant manner, however, the majority of cases occur as the result of a de novo pathogenic variant. About 10% of patients with RTS have microdeletions of chromosome 16p13.3 [Schorry 2008; PMID: 18792986]. Studies suggest haploinsufficiency as a common disease mechanism in patients with RTS with CREBBP alterations [Kung 2000, PMID: 10673499]. The etiology of the remaining cases is currently unknown. There is marked clinical variability in patients with RTS which can be explained, in part, by which gene is implicated. Individuals with pathogenic alterations in CREBBP tend to have a more severe presentation while individuals with pathogenic alterations in EP300 tend to be milder. This panel includes sequence and copy number analyses of the CREBBP and EP300 genes.
CPT Codes
81407, 81479
Collection
Collect
Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Ordering
Clinical Features
Rubinstein-Taybi syndrome (RTS) (OMIM #180849) is an autosomal dominant disorder characterized by broad thumbs and toes, distinctive facial features, postnatal growth delay, congenital heart defects and moderate to severe intellectual disability. Disease-causing alterations in both CREBBP and EP300 are currently the only genes known to be involved in RTS and the vast majority of variants are de novo. Menke-Hennekam syndrome (OMIM #618332) is an allelic phenotype associated with CREBBP and EP300, typically caused by missense variants in exons 30-31 of CRBBP or the homologous regions of EP300 [GeneReviews 2019, PMID: 20301699].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
Sequencing and copy number analysis of the genes on this panel is estimated to identify 50-60% of alterations associated with the CREBBP gene and 3-8% of alterations associated with the EP300 gene. It is estimated that about 10% of patients with RTS have microdeletions of chromosome 16p13.3 [GeneReviews 2019, PMID: 20301699].
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, and assess the risk to other first-degree relatives and to facilitate testing of at-risk family members. Molecular confirmation of a diagnosis may help guide recommendations for medical management and screening, and may help avoid unnecessary procedures.
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis is based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
CREBBP (CREB binding protein) on chromosome 16p13.3 and EP300 (E1A binding protein p300) on chromosome 22q13.2 are the only genes currently known to be associated with RTS. RTS is inherited in an autosomal dominant manner, however, the majority of cases occur as the result of a de novo pathogenic variant. About 10% of patients with RTS have microdeletions of chromosome 16p13.3 [Schorry 2008; PMID: 18792986]. Studies suggest haploinsufficiency as a common disease mechanism in patients with RTS with CREBBP alterations [Kung 2000, PMID: 10673499]. The etiology of the remaining cases is currently unknown. There is marked clinical variability in patients with RTS which can be explained, in part, by which gene is implicated. Individuals with pathogenic alterations in CREBBP tend to have a more severe presentation while individuals with pathogenic alterations in EP300 tend to be milder. This panel includes sequence and copy number analyses of the CREBBP and EP300 genes.
