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Combined Pituitary Hormone Deficiency-2 (CPHD2) via the PROP1 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
PROP1 81404 81404,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9079PROP181404 81404,81479 $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


  • Fang Xu, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Combined pituitary hormone deficiency (CPHD) is a condition that characterized by a shortage of several hormones produced by anterior pituitary. PROP1-related CPHD2 is associated with deficiencies of growth hormone (GH), thyroid-stimulating hormone (TSH), gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)), prolactin (PrL), and occasionally adrenocorticotropic hormone (ACTH) ( de Graaff et al. 2014). The clinical phenotype of PROP1-related CPHD is highly variable both within and between pedigrees with respect to the degree of pituitary hormone deficiency and the age of onset of the deficiency. Most affected individuals are ascertained because of a failure to grow and short stature starting in infancy or early childhood. People with CPHD2 may have mild hypothyroidism which could cause poor weight gain and fatigue. Other features of CPHD2 include absent or delayed puberty and incomplete secondary sexual development with infertility. Untreated males usually present hypogonadism while females often lack breast development or menses. ACTH deficiency is less common and does not occur until adulthood (Flück et al. 1998; Bottner et al. 2004].


50% of CPHD has a genetic basis and pathogenic variants in at least eight genes are found to cause genetically determined CPHD. PROP1 pathogenic variants are the most common known cause of this disorder, accounting for approximately 50% of familiar cases, although the incidence in sporadic cases is much lower (de Graaff et al. 2014). PROP1 is a pituitary-specific paired-like homeodomain transcription factor that plays a crucial role in the proper development of the pituitary gland and the specialization of its cell types (Duquesnoy et al. 1998). Pathogenic variants in PROP1 perturb ontogenesis of pituitary gonadotropes, somatotropes, lactotropes, and thyrotropes. These developmental defects result in deficiencies of LH, which is needed for normal growth; FSH and GH, which both play a role in sexual development and fetility; TSH, which helps with thyroid gland function; prolactin, which stimulates the production of breast milk; and ACTH, which influences energy production in the body and maintains normal blood sugar and blood pressure levels (Kelberman et al. 2009).

PROP1-related CPHD is inherited in an autosomal recessive manner. At least 34 pathogenic variants in the PROP1 gene have been found to cause CPHD (Human Gene Mutation Database). The most common pathogenic variant in which three AG repeats are reduced to two AG repeats (c.301_302del) deletes two DNA building blocks in the PROP1 gene and accounts for 55% of alleles in familial cases and 12% of alleles in sporadic cases of CPHD ( de Graaff et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect pathogenic variants in PROP1 in 50% of familial Combined Pituitary Hormone Deficiency and 1%-2% of sporadic CPHD (Bottner et al. 2004; Turton et al. 2005).

To date, 5 large deletions in the PROP1 gene have been reported in patients affected with CPHD (Abrão et al. 2006; Kelberman et al. 2009; Zhang et al. 2010).

Testing Strategy

This test provides full coverage of all coding exons of the PROP1 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 GH deficiency and at least one other pituitary hormone deficiency, and family members of patients with known pathogenic variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PROP1.


Official Gene Symbol OMIM ID
PROP1 601538
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Pituitary Hormone Deficiency, Combined 2 AR 262600

Related Tests

Combined Pituitary Hormone Deficiency (CPHD) Panel
Congenital Hypothyroidism and Thyroid Hormone Resistance Panel
Hypogonadotropic Hypogonadism/Kallmann Syndrome Panel


  • Abrão M.G. et al. 2006. Clinical Endocrinology 65: 294-300 PubMed ID: 16918947
  • Böttner A. et al. 2004. The Journal of Clinical Endocrinology and Metabolism. 89: 5256-65. PubMed ID: 15472232
  • Duquesnoy P. et al. 1998. Febs Letters. 437: 216-20. PubMed ID: 9824293
  • Flück C. et al. 1998. The Journal of Clinical Endocrinology and Metabolism. 83: 3727-34. PubMed ID: 9768691
  • Graaff L.C.G. 2014. PROP1-Related Combined Pituitary Hormone Deficiency. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301521
  • Human Gene Mutation Database (Bio-base).
  • Kelberman D. et al. 2009. Clinical Endocrinology. 70: 96-103. PubMed ID: 19128366
  • Turton J.P. et al. 2005. Clinical Endocrinology. 63: 10-8. PubMed ID: 15963055
  • Zhang H. et al 2010. Hormone Research in Pediatrics. 74:98-105 PubMed ID: 20395664


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