X-Linked Spondyloepiphyseal Dysplasia Tarda (SEDT) via the TRAPPC2 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
10037 TRAPPC2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10037TRAPPC281479 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

X-linked spondyloepiphyseal dysplasia tarda (SEDT; OMIM#313400) is characterized by disproportionately short stature with a short trunk and an arm span significantly greater than height. At birth, affected males are normal in length and have normal body proportions. Around age six to eight years, those affected males begin to exhibit retarded linear growth. Final adult height is typically 4'10" to 5'6". Progressive joint and back pain with osteoarthritis ensues; hip, knee, and shoulder joints are commonly involved but to a variable degree. Hip replacement is often required as early as age 40 years (Tiller & Hannig. GeneReviews. 2011).

Genetics

X-linked SEDT is inherited in an X-linked recessive manner. TRAPPC2 (previously known as SEDL) is the only gene in which variants are known to cause X-linked SEDT. TRAPPC2 encodes sedlin, an evolutionarily-conserved and ubiquitously-expressed protein whose function remains poorly understood. Based on the function of the yeast homolog, sedlin may be involved with intracellular protein trafficking, as part of the TRAPP (transport protein particle) complex (Jang et al. J Biol Chem. 277:49863–49869, 2002). Other studies have demonstrated localization of sedlin to the nucleus, where it interacts with various transcription factors (Liu et al. J Cell Biochem 109:1129–1133, 2010). Small deletions causing frameshifts and splice site variants in TRAPPC2 were found in more than half of reported X-linked SEDT cases (Savarirayan et al. Eur J Hum Genet 11:639–642, 2003). Missense and nonsense variants were a relatively less common type of variant (Gedeon et al. Am J Hum Genet 68:1386–1397, 2001). Large deletions involving single or multiple exons have also been documented in different studies (Gedeon et al. 2001; Shaw et al. Clin Genet 64:235–242, 2003; Fiedler et al. Hum Mutat 24:103, 2004), though cumulatively accounting for only a small portion of cases.

Clinical Sensitivity - Sequencing with CNV PGxome

Sequencing of TRAPPC2 is predicted to detect disease variants in more than 80% of males with a clinical diagnosis of X-linked SEDT (Gedeon et al. 2001; Fiedler et al. 2004). Note: TRAPPC2 gene deletions are suspected in males based on failed amplification of single or multiple exons. Some of these large deletions would not be detected in female carriers by sequence analysis.

Testing Strategy

This test provides full coverage of all coding exons of the TRAPPC2 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 with clinical and radiographic features consistent with X-linked SEDT and family members of patients who have known TRAPPC2 variants.

Gene

Official Gene Symbol OMIM ID
TRAPPC2 300202
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Spondyloepiphyseal Dysplasia Tarda XL 313400

Citations

  • Fiedler, J., et.al. (2004). "X-linked spondyloepiphyseal dysplasia tarda: Novel and recurrent mutations in 13 European families." Hum Mutat 24(1): 103. PubMed ID: 15221797
  • Gedeon, A. K., et.al. (2001). "The molecular basis of X-linked spondyloepiphyseal dysplasia tarda." Am J Hum Genet 68(6): 1386-97. PubMed ID: 11349230
  • Jang, S. B., et.al. (2002). "Crystal structure of SEDL and its implications for a genetic disease spondyloepiphyseal dysplasia tarda." J Biol Chem 277(51): 49863-9. PubMed ID: 12361953
  • Liu, X., et.al. (2010). "Interaction of Sedlin with PAM14." J Cell Biochem 109(6): 1129-33. PubMed ID: 20108251
  • Savarirayan, R., et.al. (2003). "Spondyloepiphyseal dysplasia tarda (SEDL, MIM #313400)." Eur J Hum Genet 11(9): 639-42. PubMed ID: 12939648
  • Shaw, M. A., et.al. (2003). "Identification of three novel SEDL mutations, including mutation in the rare, non-canonical splice site of exon 4." Clin Genet 64(3): 235-42. PubMed ID: 12919139
  • Tiller, George E MD, PhD (2011). "X-Linked Spondyloepiphyseal Dysplasia Tarda."

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

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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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