DNA icon

Distal Arthrogryposis 2B (Sheldon-Hall Syndrome) via the TNNT3 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
11757 TNNT3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11757TNNT381479 81479,81479 $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.

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).

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

For Sanger Sequencing click here.

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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Distal arthrogryposis (DA) syndromes are a group of multiple congenital contracture disorders with distal joint involvement, variable clinical expression, and autosomal dominant inheritance (Bamshad et al. Am J Med Genet 65:277-281, 1996). Clinically, Sheldon-Hall syndrome is intermediate between Freeman-Sheldon syndrome (FSS; DA2A, OMIM 193700) and TPM2-related DA (DA1; OMIM 108120). Initially, individuals with findings shared by both DA1 and Freeman-Sheldon syndrome were classified as variant Freeman-Sheldon syndrome (Krakowiak et al. 1997) but are now known as Sheldon-Hall syndrome or DA2B (OMIM 601680). Sheldon-Hall syndrome is the most common DA syndrome. Facial features in Sheldon-Hall syndrome are reminiscent of, but less pronounced than, those of Freeman-Sheldon syndrome. Patients have been described with mild micrognathia and narrow palpebral fissures (Kimber et al. Neurology 67:597-601, 2006). The original phenotypic description included triangular face, down-slating palpebral fissures, prominent nasolabial folds, and small mouth (Krakowiak et al. Am J Hum Genet 60:426-432, 1997). Notably, Sheldon-Hall syndrome patients lack the whistling-like appearance universal among Freeman-Sheldon syndrome patients. Skeletal findings include severe camptodactyly, ulnar deviation, and club foot or flexible flatfoot (Sung et al. Am J Hum Genet 72:681-690, 2003). Remarkable variation in phenotypic manifestation has been described (Shrimpton and Hoo. Eur J Hum Genet 49:201-206, 2006).

Genetics

Distal arthrogryposis 2B (Sheldon-Hall syndrome) is inherited as an autosomal dominant disorder due to variants in the TNNI2, TNNT3, and MYH3 genes. In the TNNT3 gene, one missense variant (p.Arg63His) has been identified in a family with Sheldon-Hall syndrome.

The troponin T fast skeletal protein is coded by the TNNT3 gene (OMIM 600692) located on chr 11p15.

Clinical Sensitivity - Sequencing with CNV PGxome

TNNT3 appears to be a rare cause of Sheldon-Hall syndrome. Among 47 DA families, one was found to have a TNNT3 variant (Sung et al. Amer J Hum Genet 73:212-214, 2003).

Testing Strategy

This test provides full coverage of all coding exons of the TNNT3 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. 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

Individuals with clinical symptoms consistent with distal arthrogryposis and facial features consistent with Sheldon-Hall syndrome.

Gene

Official Gene Symbol OMIM ID
TNNT3 600692
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Arthrogryposis, Distal, Type 2B AD 601680

Citations

  • Bamshad M. et al. 1996. American Journal of Medical Genetics. 65: 277-81. PubMed ID: 8923935
  • Kimber, E., et.al. (2006). "A mutation in the fast skeletal muscle troponin I gene causes myopathy and distal arthrogryposis." Neurology 67(4): 597-601. PubMed ID: 16924011
  • Krakowiak, P. A., et.al. (1997). "A variant of Freeman-Sheldon syndrome maps to 11p15.5-pter." Am J Hum Genet 60(2): 426-32. PubMed ID: 9012416
  • Shrimpton, A. E., Hoo, J. J. (2006). "A TNNI2 mutation in a family with distal arthrogryposis type 2B." Eur J Med Genet 49(2): 201-6. PubMed ID: 16497570
  • Sung S.S. et al. 2003. American Journal of Human Genetics. 72: 681-90. PubMed ID: 12592607
  • Sung, S. S., et.al. (2003). "Mutations in TNNT3 cause multiple congenital contractures: a second locus for distal arthrogryposis type 2B." Am J Hum Genet 73(1): 212-4. PubMed ID: 12865991

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
×