CDC73-Related Disorders via the CDC73 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 4575 | CDC73 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
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.
Clinical Features and Genetics
Clinical Features
CDC73-related disorders include hyperparathyroidism-jaw tumor syndrome (HPT-JT), parathyroid carcinoma, and familial isolated hyperparathyroidism (FIHP). The most common feature to these disorders is hyperparathyroidism. Patients are often symptomatic in late adolescence to early adulthood and show severe hypercalcemia (Frank-Raue et al. Eur J Endocrinol 165(3): 477-483, 2011). The etiology from these affected individuals is usually a single parathyroid adenoma, and less frequently a parathyroid carcinoma (10-15%) (Rich et al. GeneReviews, 2008; Frank-Raue et al. 2011). Approximately 30-40% of affected individuals have a benign ossified fibroma in the mandible or maxilla. Other growths include renal cysts and hamartomas, and less frequently Wilms tumor (Masi et al. Endocr Relat Cancer 15(4): 1115–1126, 2008). Females with HPT-JT syndrome are also at risk of benign and malignant uterine cancer (Rich et al. GeneReviews, 2008).
Genetics
CDC73-related disorders are inherited in an autosomal dominant manner and are caused by mutations in the CDC73 gene (formerly known as HRPT2). CDC73 encodes parafibromin, which is a tumor suppressor (Bradley et al. Clin Endocrinol 64(3): 299-306, 2006) that is involved in regulating the cell cycle and gene expression (Masi et al., 2008). Most cases of CDC73-related disorders are inherited from an affected parent, although rarely sporadic cases and germline mosaicism have also been reported. CDC73-related disorders show incomplete penetrance and varied expressivity (Frank-Raue et al. Eur J Endocrinol 165(3): 477-483, 2011). Most mutations result in truncated proteins due to nonsense mutations, but other mutations such as missense, splice site changes, small insertions and duplications, and gross deletions and a duplication have also been reported throughout the gene (Human Gene Mutation Database). Somatic CDC73 mutations are also observed in parathyroid tumors from individuals with HPT-JT and FIHP (Masi et al. 2008).
Clinical Sensitivity - Sequencing with CNV PG-Select
Approximately 60% of individuals with HPT-JT will have a mutation in the CDC73 gene (Carpten et al. Nat Genet 32(4):676-680, 2002), and 20-33% of individuals with sporadic parathyroid carcinoma (Shattuck et al. N Eng J Med 349(18): 1722-1729, 2003; Masi et al. Endocr Relat Cancer 15(4):1115–1126, 2008). CDC73 mutations are a rare cause of FIHP, but can been seen in up to 7% of cases (Villablanca et al. J Med Genet 41(3): e32, 2004; Masi et al. 2008).
Clinical sensitivity for CNV detection is unknown at this time, but gross deletions in CDC73 have been reported (Bricaire L. et al. J Clin Endocrinol Metab 98(2): E403-E408, 2013; Cascón A. et al. Genes Chromosomes Cancer 50(11): 922-929, 2011; Domingues R. et al. Clin Endocrinol (Oxf) 76(1): 33-38, 2012).
Testing Strategy
This test provides full coverage of all coding exons of the CDC73 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
This test is useful for individuals who have biochemical findings of primary hyperparathyroidism, ossifying fibroma(s) of the maxilla and/or mandible, and/or familial/sporadic parathyroid carcinoma or adenoma. Testing for CDC73 mutations for parathyroid lesions may be performed if testing for MEN1 mutations is negative, and less commonly if RET testing is negative. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
This test is useful for individuals who have biochemical findings of primary hyperparathyroidism, ossifying fibroma(s) of the maxilla and/or mandible, and/or familial/sporadic parathyroid carcinoma or adenoma. Testing for CDC73 mutations for parathyroid lesions may be performed if testing for MEN1 mutations is negative, and less commonly if RET testing is negative. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| CDC73 | 607393 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Hyperparathyroidism 1 | AD | 145000 |
| Hyperparathyroidism 2 | AD | 145001 |
| Parathyroid Carcinoma | AD | 608266 |
Related Test
| Name |
|---|
| Renal Cancer Panel |
Citations
- Bradley et al. 2006. Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours. Clin Endocrinol 64(3): 299-306. PubMed ID: 16487440
- Bricaire L, Odou M-F, Cardot-Bauters C, Delemer B, North M-O, Salenave S, Vezzosi D, Kuhn J-M, Murat A, Caron P, Sadoul J-L, Silve C, et al. 2013. Frequent large germline HRPT2 deletions in a French National cohort of patients with primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 98: E403–408. PubMed ID: 23293331
- Carpten JD, Robbins CM, Villablanca A, Forsberg L, Presciuttini S, Bailey-Wilson J, Simonds WF, Gillanders EM, Kennedy AM, Chen JD, Agarwal SK, Sood R, et al. 2002. HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat. Genet. 32: 676–680. PubMed ID: 12434154
- Cascón A. et al. (2011). "Detection of the first gross CDC73 germline deletion in an HPT-JT syndrome family." Genes Chromosomes Cancer 50(11): 922-929. PubMed ID: 21837707
- Domingues R, Tomaz RA, Martins C, Nunes C, Bugalho MJ, Cavaco BM. 2012. Identification of the first germline HRPT2 whole-gene deletion in a patient with primary hyperparathyroidism. Clin. Endocrinol. (Oxf) 76: 33–38. PubMed ID: 21790700
- Frank-Raue et al. (2011). "CDC73-related hereditary hyperparathyroidism: five new mutations and the clinical spectrum." Eur J Endocrinol 165(3): 477-483. PubMed ID: 21652691
- Human Gene Mutation Database (Bio-base).
- Masi et al. 2008. Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism. Endocr Relat Cancer 15(4): 1115–1126. PubMed ID: 18755853
- Rich et al. (2008). "CDC73-Related Disorders." GeneReviews. PubMed ID: 20301744
- Shattuck TM, Välimäki S, Obara T, Gaz RD, Clark OH, Shoback D, Wierman ME, Tojo K, Robbins CM, Carpten JD. 2003. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. New England Journal of Medicine 349: 1722–1729. PubMed ID: 14585940
- Villablanca A. 2004. Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP). Journal of Medical Genetics 41: 32e–32. PubMed ID: 14985403
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
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
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