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Hydroxyprolinemia via the PRODH2 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
9925 PRODH2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9925PRODH281479 81479(x2) $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.

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

18 days on average for standard orders or 13 days 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

  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Hydroxyprolinemia is an inborn error of amino acid metabolism that is caused by deficient hydroxyproline degradation. Thus far, no clinical phenotype has been associated with hydroxyprolinemia, and it is therefore considered most likely to be a benign biochemical disorder. However, it is difficult to differentiate between hydroxyproline and leucine, isoleucine and alloisoleucine via tandem mass spectrometry (MS/MS), a common technique used for newborn screening (NBS). As elevated levels of leucine, isoleucine and alloisoleucine are suggestive of maple syrup urine disease (MSUD), it is possible that individuals with hydroxyprolinemia may have a false positive NBS result suggestive of MSUD. For patients with positive NBS results for MSUD yet no positive molecular diagnosis, molecular testing for hydroxyprolinemia may be helpful (Staufner et al. 2016. PubMed ID: 27139199).

Genetics

Hydroxyprolinemia is a rare autosomal recessive inborn error of metabolism caused by pathogenic sequence variants in the PRODH2 gene, which is located on chromosome 19 at 19q13.12. In the only molecular study of PRODH2 performed to date, molecularly confirmed hydroxyprolinemia was reported to be at least 2.5 times more prevalent than MSUD (estimates of ~1/23,000 to 1/47,000 for hydroxyprolinemia compared to ~1/121,000 for MSUD) (Staufner et al. 2016. PubMed ID: 27139199). Reported causative variants in PRODH2 are mainly missense, although in-frame deletions, nonsense and frameshift variants have also been identified (Staufner et al. 2016. PubMed ID: 27139199).

The PRODH2 gene encodes the enzyme proline dehydrogenase, which is responsible for the first step of hydroxyproline breakdown. Hydroxyproline is a major component of collagen. Based on recent insights into the mechanism of this enzyme, it has been suggested that the gene name be changed to HYPDH (hydroxyproline dehydrogenase) (Staufner et al. 2016. PubMed ID: 27139199).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only a small number of patients have been reported. Analytical sensitivity should be high because the great majority of pathogenic variants reported are detectable by sequencing (Staufner et al. 2016. PubMed ID: 27139199).

Testing Strategy

This test provides full coverage of all coding exons of the PRODH2 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

Patients with hydroxyprolinemia as well as those with apparent false positive NBS results suggestive of MSUD are good candidates for this test. Family members of patients who have known PRODH2 pathogenic variants are also good candidates. We will also sequence the PRODH2 gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
PRODH2 616377
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID

Citations

  • Staufner et al. 2016. PubMed ID: 27139199

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

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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: $
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