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Rubinstein-Taybi Syndrome via the CREBBP Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
CREBBP 81407 81407,81406 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15153CREBBP81407 81407,81406 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Rubinstein-Taybi syndrome (also called broad Thumbs-Hallux Syndrome) is characterized by short stature, distinctive facial features, broad thumbs and big toes, moderate to severe intellectual disability and postnatal growth retardation. Other features include cryptorchidism, microcephaly, speech delay, delayed bone age, gastroesophageal reflux, coloboma, renal abnormalities and congenital heart defects. The prevalence is ~ 1/125,000 live births (Stevens 2014; Milani et al. 2015).


Rubinstein-Taybi syndrome is inherited in an autosomal dominant manner and is caused by pathogenic variants in the CREBBP and EP300 genes. ~250 unique CREBBP pathogenic variants have been reported. They include: missense (16%), nonsense (16%), splicing (8%), small deletion/insertion (29%), gross deletion (19%), gross duplication (10%) and 3 unique translocations involving CREBBP (Petrij et al. 2000; Thienpont et al. 2007; Tsai et al. 2011; Demeer et al. 2013). CREBBP intragenic deletions were identified in 7 out of 75 patients with Rubinstein–Taybi syndrome by MLPA analysis (Aradhya et al. 2012). Interstitial 16p13.3 duplications of the critical Rubinstein region were found in patients with intellectual disability & multiple congenital anomalies, and 8 out of 9 of these duplications arose de novo (Thienpont et al. 2010; Demeer et al. 2013). CREBBP and EP300 proteins, coded by CREBBP and EP300, respectively, are transcriptional adaptors and histone acetyltransferases that acetylate nucleosomes (Ogryzko et al. 1996).

Clinical Sensitivity - Sequencing with CNV PG-Select

Sequence analysis can detect CREBBP pathogenic variants in 40%-50% of Rubinstein-Taybi syndrome cases. 16p13.3 microdeletions (size ranging from 3.3kb to 3900kb) involving CREBBP were found 17 out of 83 patients with typical features of Rubinstein–Taybi syndrome using array CGH and quantitative multiplex fluorescent-PCR (Stef et al. 2007).

Testing Strategy

This test is performed using Next-Generation sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the CREBBP gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with symptoms consistent with Rubinstein-Taybi syndrome, and the family members of patients who have known CREBBP pathogenic variants (Stevens 2014).


Official Gene Symbol OMIM ID
CREBBP 600140
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Rubinstein-Taybi Syndrome AD 180849


  • Aradhya S, Lewis R, Bonaga T, Nwokekeh N, Stafford A, Boggs B, Hruska K, Smaoui N, Compton JG, Richard G, Suchy S. 2012. Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders. Genetics in Medicine 14: 594-603. PubMed ID: 22382802
  • Demeer B, Andrieux J, Receveur A, Morin G, Petit F, Julia S, Plessis G, Martin-Coignard D, Delobel B, Firth HV, Thuresson AC, Lanco dosen S, Sjörs K, Le Caignec C, Devriendt K, Mathieu-Dramard M. 2013. Duplication 16p13.3 and the CREBBP gene: Confirmation of the phenotype. European Journal of Medical Genetics 56: 26-31. PubMed ID: 23063576
  • Milani D, Manzoni FMP, Pezzani L, Ajmone P, Gervasini C, Menni F, Esposito S. 2015. Rubinstein-Taybi syndrome: clinical features, genetic basis, diagnosis, and management. Ital J Pediatr 41: PubMed ID: 4308897
  • Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y. 1996. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87: 953-959. PubMed ID: 8945521
  • Petrij F, Dorsman JC, Dauwerse HG, Giles RH, Peeters T, Hennekam RCM, Breuning MH, Peters DJM. 2000. Rubinstein-Taybi syndrome caused by a de novo reciprocal translocation t(2;16)(q36.3;p13.3). Am. J. Med. Genet. 92: 47-52. PubMed ID: 10797422
  • Stef M, Simon D, Mardirossian B, Delrue M-A, Burgelin I, Hubert C, Marche M, Bonnet F, Gorry P, Longy M, Lacombe D, Coupry I, Arveiler B. 2007. Spectrum of CREBBP gene dosage anomalies in Rubinstein–Taybi Syndrome patients. Eur J Hum Genet 15: 843–847. PubMed ID: 17473832
  • Stevens CA. 2014. Rubinstein-Taybi Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301699
  • Thienpont B, Béna F, Breckpot J, Philip N, Menten B, Esch HV, Scalais E, Salamone JM, Fong C-T, Kussmann JL, Grange DK, Gorski JL, Zahir F, Yong SL, Morris MM, Gimelli S, Fryns JP, Mortier G, Friedman JM, Villard L, Bottani A, Vermeesch JR, Cheung SW, Devriendt K. 2010. Duplications of the critical Rubinstein-Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome. J Med Genet 47: 155-161. PubMed ID: 19833603
  • Thienpont B, Breckpot J, Holvoet M, Vermeesch JR, Devriendt K. 2007. A microduplication of CBP in a patient with mental retardation and a congenital heart defect. Am. J. Med. Genet. 143A: 2160-2164. PubMed ID: 17702016
  • Tsai AC-H, Dossett CJ, Walton CS, Cramer AE, Eng PA, Nowakowska BA, Pursley AN, Stankiewicz P, Wiszniewska J, Cheung SW. 2011. Exon deletions of the EP300 and CREBBP genes in two children with Rubinstein-Taybi syndrome detected by aCGH. Eur. J. Hum. Genet. 19: 43-49. PubMed ID: 20717166


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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