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Camurati-Engelmann Disease (CED) via the TGFB1 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
TGFB1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8507TGFB181479 81479,81479 $990 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 platform).

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

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.


Genetic Counselors


  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Camurati-Engelmann disease (OMIM#131300) is characterized by hyperostosis of the long bones and the skull; proximal muscle weakness; severe limb pain; a wide-based, waddling gait; and joint contractures. Facial features such as frontal bossing, enlargement of the mandible, proptosis, and cranial nerve impingement resulting in facial palsy are seen in severely affected individuals later in life (Wallace & Wilcox. GeneReview. 2010). Rare manifestations include anemia, anorexia, hepatosplenomegaly, decreased subcutaneous tissue, atrophic skin, hyperhidrosis of the hands and feet, delayed dentition, extensive caries, delayed puberty, and hypogonadism (Gupta & Cheikh. Endocr Pract. 11:399–407, 2005).


Camurati-Engelmann disease is inherited in an autosomal dominant manner with reduced penetrance. TGFB1 is the only gene known to be associated with CED. TGFB1 encodes transforming growth factor beta-1 (TGF-β1), a large precursor molecule and a multifunctional peptide that controls proliferation, differentiation, and other functions in many cell types. TGF-β1 preprotein contains a signal peptide of 29 amino acids that is proteolytically cleaved. TGF-β1 is further cleaved after amino acid 278 to form latency-associated peptide (LAP) and active TGF-β1. LAP dimerizes with interchain disulfide links at Cys223 and Cys225. TGF-β1 can be secreted as an inactive small latent complex that consists of a mature TGF-β1 homodimer non-covalently associated with an LAP homodimer. The majority of pathogenic TGFB1 variants in individuals with CED lead to single amino-acid substitutions near the site of interchain disulfide bonds between the LAP homodimers. Three variants in exon 4 (p.Arg218Cys, p.Arg218His, p.Cys225Arg) account for ~80% of the total variants observed in CED (Campos-Xavier et al. Hum Genet 109:653–658, 2001). These variants may disrupt dimerization of LAP and binding to active TGF-β1, leading to increased active TGF-β1 release from the cell (Janssens et al. J Biol Chem 278:7718–7724, 2003; Kinoshita et al. Am J Med Genet 127A:104–107, 2004).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect disease variants in >90% of individuals with a clinical diagnosis of CED (Janssens et al. Nat Genet 26:273–275, 2000; Kinoshita et al. Nat Genet 26:19–20, 2000; Campos-Xavier et al. Hum Genet 109:653–658, 2001; Mumm et al. Am J Hum Genet 69S:593, 2001; Wallace et al. Am J Med Genet 129A:235–247, 2004; Janssens et al. J Med Genet 43:1–11, 2006).

Testing Strategy

This test provides full coverage of all coding exons of the TGFB1 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

Candidates for this test are patients with clinical and radiographic findings consistent with CED and family members of patients who have a known TGFB1 variant.


Official Gene Symbol OMIM ID
TGFB1 190180
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Camurati-Engelmann Disease AD 131300


  • Campos-Xavier, B., et.al. (2001). "Phenotypic variability at the TGF-beta1 locus in Camurati-Engelmann disease." Hum Genet 109(6): 653-8. PubMed ID: 11810278
  • Gupta, S., Cheikh, I. E. (2005). "Camurati-Engelmann disease in conjunction with hypogonadism." Endocr Pract 11(6): 399-407. PubMed ID: 16638728
  • Janssens, K., et.al. (2000). "Mutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease." Nat Genet 26(3): 273-5. PubMed ID: 11062463
  • Janssens, K., et.al. (2003). "Transforming growth factor-beta 1 mutations in Camurati-Engelmann disease lead to increased signaling by altering either activation or secretion of the mutant protein." J Biol Chem 278(9): 7718-24. PubMed ID: 12493741
  • Janssens, K., et.al. (2006). "Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment." J Med Genet 43(1): 1-11. PubMed ID: 15894597
  • Kinoshita, A., et.al. (2000). "Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease." Nat Genet 26(1): 19-20. PubMed ID: 10973241
  • Kinoshita, A., et.al. (2004). "TGFB1 mutations in four new families with Camurati-Engelmann disease: confirmation of independently arising LAP-domain-specific mutations." Am J Med Genet A 127A(1): 104-7. PubMed ID: 15103729
  • Mumm, S.R. (2001). "Camurati-Engelmann diesease: New mutation in the latency-associated peptide of the transforming growth factor b-1 gene."." Am J Hum Genet 69S: 593."
  • Stephanie E Wallace (2010). "Camurati-Engelmann Disease."
  • Wallace, S. E., et.al. (2004). "Marked phenotypic variability in progressive diaphyseal dysplasia (Camurati-Engelmann disease): report of a four-generation pedigree, identification of a mutation in TGFB1, and review." Am J Med Genet A 129A(3): 235-47. PubMed ID: 15326622


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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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2) Select Additional Test Options

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