Holt-Oram Syndrome (HOS) via the TBX5 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8475 TBX5 81405 81405,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8475TBX581405 81405, 81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Holt-Oram syndrome (OMIM#142900) is a developmental disorder characterized by upper-extremity malformations involving radial, thenar, or carpal bones; congenital heart malformation, most commonly ostium secundum atrial septal defect (ASD) and ventricular septal defect (VSD); or cardiac conduction disease (Newbury-Ecob et al. J Med Genet 33: 300-307, 1996). An abnormal carpal bone is present in all affected individuals and may be the only evidence of disease. HOS is the most common of the heart-hand syndromes, affecting individuals from different racial and ethnic groups.

Genetics

HOS is inherited in an autosomal dominant manner with marked intra- and interfamilial variation. Approximately 85% of affected individuals have HOS as the result of de novo variants. The upper-limb malformations in HOS are fully penetrant, while congenital heart malformations occur in ~75% of affected individuals. TBX5 gene is the only gene known to be associated with HOS. The majority of reported variants are frameshift, missense, nonsense, and splice-site variants. Deletion of an exon(s) or the entire TBX5 gene was detected in <1% of HOS individuals (Borozdin et al. Hum Mutat 27:975–976, 2006). TBX5 encodes T-Box 5, a member of the T-box family of transcription factors that has an important role in both cardiogenesis and limb development (Basson et al. Nat Genet 15:30–35, 1997). Its T-box domain, which is the DNA binding region, is highly conserved across species and among members of the T-box family. Missense variants at the 5' end of the T-box tend to be associated with more serious cardiac defects; missense variants at the 3' end of the T-box result in more pronounced limb defects (Basson et al. Nat Genet 15:30–35, 1997; Brassington et al. Am J Hum Genet 73:74–85, 2003).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect disease variants in >70% of individuals who meet strict diagnostic criteria for HOS (McDermott et al. i 58:981–986, 2005). Lower variant detection rates (30%-40%) reported in some studies (Cross et al. J Med Genet 37:785–787. 2000, Brassington et al. Am J Hum Genet 73:74–85, 2003) can be explained by the inclusion in patient cohorts of subjects who may not meet strict HOS diagnostic criteria.

Testing Strategy

This test provides full coverage of all coding exons of the TBX5 gene 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 full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients showing features consistent with HOS (evaluated via echocardiography, ECG, and hand x-rays) and family members of patients who have known TBX5 variants.

Gene

Official Gene Symbol OMIM ID
TBX5 601620
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Holt-Oram Syndrome AD 142900

Related Test

Name
Comprehensive Cardiology Panel

Citations

  • Basson, C. T., et.al. (1997). "Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome." Nat Genet 15(1): 30-5. PubMed ID: 8988165
  • Borozdin, W., et.al. (2006). "Expanding the spectrum of TBX5 mutations in Holt-Oram syndrome: detection of two intragenic deletions by quantitative real time PCR, and report of eight novel point mutations." Hum Mutat 27(9): 975-6. PubMed ID: 16917909
  • Brassington, A. M., et.al. (2003). "Expressivity of Holt-Oram syndrome is not predicted by TBX5 genotype." Am J Hum Genet 73(1): 74-85. PubMed ID: 12789647
  • Cross, S. J., et.al. (2000). "The mutation spectrum in Holt-Oram syndrome." J Med Genet 37(10): 785-7. PubMed ID: 11183182
  • McDermott, D. A., et.al. (2005). "TBX5 genetic testing validates strict clinical criteria for Holt-Oram syndrome." Pediatr Res 58(5): 981-6. PubMed ID: 16183809
  • Newbury-Ecob, R. A., et.al. (1996). "Holt-Oram syndrome: a clinical genetic study." J Med Genet 33(4): 300-7. PubMed ID: 8730285

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.

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

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ORDER OPTIONS

View Ordering Instructions

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.

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