Osteogenesis Imperfecta via the P3H1 / LEPRE1 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 8251 | P3H1 | 81479 | 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.
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.
Clinical Features and Genetics
Clinical Features
Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous skeletal disorder characterized by frequent bone fractures with or without minimal trauma. Clinical signs of OI can range from mild to severe. In addition to bone fractures, patients may have scoliosis, bowing of long bones, short stature, blue sclera, hearing loss, dentin defects, muscle weakness or joint laxity. The incidence is approximately 6-7/100,000 (Dijk et al. 2012). ~90% of clinically diagnosed OI is caused by mutations in the COL1A1 and COL1A2 genes, while ~10% is caused by mutations in the CRTAP, FKB10, P3H1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, IFITM5, BMP1, TMEM38B and other undefined genes (Dijk et al. 2012; Valadares et al. 2014).
Genetics
Mutations in the P3H1 (also known as LEPRE1) gene cause a rare severe form of autosomal recessive type VIII OI, which is characterized by white sclerae, severe growth deficiency, extreme skeletal undermineralization, and bulbous metaphyses. LEPRE1 belongs to a family of collagen prolyl hydroxylases which are required in collagen biosynthesis, proper folding and protein assembly. To date, more than 20 unique causative mutations have been identified. They are mainly nonsense, splicing site and small deletion/insertion. Only one large deletion and one missense mutation in the P3H1 gene have been reported (Cabral et al. 2007; Baldridge et al. 2008; Caparrós-Martin et al. 2013; Human Gene Mutation Database).
Clinical Sensitivity - Sequencing with CNV PGxome
P3H1 mutations were identified in 2 out of 10 clinically diagnosed autosomal recessive OI families (Caparrós-Martin et al. 2013).
Testing Strategy
This test provides full coverage of all coding exons of the P3H1 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 symptoms consistent with autosomal recessive OI type VIII, who have no mutations in the COL1A1 and COL1A2 genes and the family members of patients who have known P3H1 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in P3H1.
Candidates for this test are patients with symptoms consistent with autosomal recessive OI type VIII, who have no mutations in the COL1A1 and COL1A2 genes and the family members of patients who have known P3H1 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in P3H1.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| P3H1 | 610339 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Osteogenesis Imperfecta, Type VIII | AR | 610915 |
Citations
- Baldridge D, Schwarze U, Morello R, Lennington J, Bertin TK, Pace JM, Pepin MG, Weis M, Eyre DR, Walsh J, Lambert D, Green A, et al. 2008. CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Hum Mutat 29: 1435-1442. PubMed ID: 18566967
- Cabral WA, Chang W, Barnes AM, Weis M, Scott MA, Leikin S, Makareeva E, Kuznetsova NV, Rosenbaum KN, Tifft CJ, Bulas DI, Kozma C, et al. 2008. Corrigendum: Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. Nat Genet 40: 927-927. PubMed ID: 17277775
- Caparrós-Martin JA, Valencia M, Pulido V, MartÃnez-Glez V, Rueda-Arenas I, Amr K, Farra C, Lapunzina P, Ruiz-Perez VL, Temtamy S, Aglan M. 2013. Clinical and molecular analysis in families with autosomal recessive osteogenesis imperfecta identifies mutations in five genes and suggests genotype-phenotype correlations. Am. J. Med. Genet. A 161A: 1354-1369. PubMed ID: 23613367
- Dijk FS Van, Byers PH, Dalgleish R, Malfait F, Maugeri A, Rohrbach M, Symoens S, Sistermans EA, Pals G. 2012. EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta. European Journal of Human Genetics 20: 11-19. PubMed ID: 21829228
- Human Gene Mutation Database (Bio-base).
- Valadares ER, Carneiro TB, Santos PM, Oliveira AC, Zabel B. 2014. What is new in genetics and osteogenesis imperfecta classification? Jornal de Pediatria 90:536-41. PubMed ID: 25046257
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
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
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ORDER OPTIONS
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2) Select Additional Test Options
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