DNA icon

Rubinstein-Taybi Syndrome and Floating-Harbor Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10141 CREBBP 81407,81406 Order Options and Pricing
EP300 81479,81479
SRCAP 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10141Genes x (3)81479 81406(x1), 81407(x1), 81479(x4) $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Hannah Cox, PhD

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).

Floating-Harbor syndrome is a rare short stature syndrome with delayed osseous maturation, expressive language impairments, typical facial dysmorphism, and intellectual disability (Nikkel et al. 2013). Floating-Harbor syndrome shares some features with Rubinstein-Taybi syndrome, such as short stature, a long nose with low-hanging columella, a thin vermilion border of the upper lip, and anomalous thumbs.

Genetics

Rubinstein-Taybi syndrome is inherited in an autosomal dominant manner and is caused by pathogenic variants in the CREBBP and EP300 genes.

Floating-Harbor syndrome is inherited in an autosomal dominant manner and is caused by pathogenic variants in the SRCAP gene.

~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 9 these duplications arose de novo (Thienpont et al. 2010; Demeer et al. 2013).

Less than 20 unique EP300 pathogenic variants for Rubinstein-Taybi syndrome have been reported. They include: nonsense (2), splicing (1), small deletion and duplication (8), and large deletion involving single or multiple exons (5) (Tsai et al. 2011; Roelfsema et al. 2005; Solomon et al. 2015 and Negri et al. 2015). Most pathogenic variants in the EP300 gene occur de novo (Woods et al. 2014).

CREBBP and EP300 proteins, coded by CREBBP and EP300, respectively, are transcriptional adaptors and histone acetyltransferases that acetylate nucleosomes (Ogryzko et al. 1996).

SRCAP is an SNF2-related chromatin-remodeling factor that serves as a coactivator for CREBBP, the major gene for Rubinstein-Taybi syndrome. All the reported pathogenic variants are located in exon 34 resulting in truncation of SRCAP protein (nonsense: 32%, small deletion/insertion: 68%) except one in exon 33. The c.7330C>T, p.Arg2444* and c.7303C>T, p.Arg2435* are recurrent variants which were found in about 46% and 25% of the studied patients, respectively (Nikkel et al. 2013). At least 5 out of 13 patients had a de novo pathogenic variant (Hood et al. 2012). No large deletions and insertions have been identified.

Clinical Sensitivity - Sequencing with CNV PGxome

Sequence analysis can detect CREBBP pathogenic variants in 40%-50% of Rubinstein-Taybi syndrome cases. Pathogenic variants in EP300 are identified in ~3%-8% of patients with Rubinstein–Taybi syndrome (Stevens 2014). 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). In one study, SRCAP pathogenic variants were found in 6 out of 9 patients with Floating-Harbor syndrome (Le Goff et al. 2013).

Testing Strategy

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

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with symptoms consistent with Rubinstein-Taybi syndrome, Floating-Harbor syndrome and family members of patients who have known CREBBP, EP300 and SRCAP pathogenic variants (Stevens 2014; Hood et al. 2012).

Genes

Official Gene Symbol OMIM ID
CREBBP 600140
EP300 602700
SRCAP 611421
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • 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
  • Hood RL, Lines MA, Nikkel SM, Schwartzentruber J, Beaulieu C, Nowaczyk MJM, Allanson J, Kim CA, Wieczorek D, Moilanen JS, Lacombe D, Gillessen-Kaesbach G, Whiteford ML, Quaio CR, Gomy I, Bertola DR, Albrecht B, Platzer K, McGillivray G, Zou R, McLeod DR, Chudley AE, Chodirker BN, Marcadier J; FORGE Canada Consortium, Majewski J, Bulman DE, White SM, Boycott KM. 2012. Mutations in SRCAP, Encoding SNF2-Related CREBBP Activator Protein, Cause Floating-Harbor Syndrome. Am J Hum Genet 90: 308-313. PubMed ID: 22265015
  • Le Goff C, Mahaut C, Bottani A, Doray B, Goldenberg A, Moncla A, Odent S, Nitschke P, Munnich A, Faivre L, Cormier-Daire V. 2013. Not All Floating-Harbor Syndrome Cases are Due to Mutations in Exon 34 of SRCAP. Human Mutation 34: 88–92. PubMed ID: 22965468
  • 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
  • Negri G, Milani D, Colapietro P, Forzano F, Della Monica M, Rusconi D, Consonni L, Caffi LG, Finelli P, Scarano G, Magnani C, Selicorni A, Spena S, Larizza L, Gervasini C. 2015. Clinical and molecular characterization of Rubinstein-Taybi syndrome patients carrying distinct novel mutations of the EP300 gene. Clin Genet 87: 148-154. PubMed ID: 24476420
  • Nikkel SM, Dauber A, Munnik S de, Connolly M, Hood RL, Caluseriu O, Hurst J, Kini U, Nowaczyk MJM, Afenjar A, Albrecht B, Allanson JE, Balestri P, Ben-Omran T, Brancati F, Cordeiro I, da Cunha BS, Delaney LA, Destrée A, Fitzpatrick D, Forzano F, Ghali N, Gillies G, Harwood K, Hendriks YM, Héron D, Hoischen A, Honey EM, Hoefsloot LH, Ibrahim J, Jacob CM, Kant SG, Kim CA, Kirk EP, Knoers NV, Lacombe D, Lee C, Lo IF, Lucas LS, Mari F, Mericq V, Moilanen JS, Møller ST, Moortgat S, Pilz DT, Pope K, Price S, Renieri A, Sá J, Schoots J, Silveira EL, Simon ME, Slavotinek A, Temple IK, van der Burgt I, de Vries BB, Weisfeld-Adams JD, Whiteford ML, Wierczorek D, Wit JM, Yee CF, Beaulieu CL; FORGE Canada Consortium, White SM, Bulman DE, Bongers E, Brunner H, Feingold M, Boycott KM. 2013. The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP. Orphanet J Rare Dis 8: 63. PubMed ID: 23621943
  • 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
  • Roelfsema JH, White SJ, Ariyürek Y, Bartholdi D, Niedrist D, Papadia F, Bacino CA, Dunnen JT den, Ommen G-JB van, Breuning MH, Hennekam RC, Peters DJM. 2005. Genetic Heterogeneity in Rubinstein-Taybi Syndrome: Mutations in Both the CBP and EP300 Genes Cause Disease. Am J Hum Genet 76: 572-580. PubMed ID: 15706485
  • Solomon BD, Bodian DL, Khromykh A, Mora GG, Lanpher BC, Iyer RK, Baveja R, Vockley JG, Niederhuber JE. 2015. Expanding the phenotypic spectrum in EP300-related Rubinstein-Taybi syndrome. Am. J. Med. Genet. 167: 1111-1116. PubMed ID: 25712426
  • 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
  • Woods S.A. et al. 2014. American Journal of Medical Genetics. Part A. 164A: 251-8. PubMed ID: 24352918

Ordering/Specimens

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
×
Copy Text to Clipboard
×