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Osteogenesis Imperfecta via the IFITM5 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
9211 IFITM5 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9211IFITM581479 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

  • Juan Dong, PhD, FACMG

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, and 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, and ~10% is caused by mutations in the CRTAP, FKB10, LEPRE1, 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 IFITM5 gene cause autosomal dominant type V OI. Type V OI consists of ~4-5% of OI cases and is characterized by interosseous membrane calcification of the forearm and hyperplastic callus formation with variable clinical expressions (Rauch et al. 2004). IFITM5 protein (interferon induced transmembrane protein 5) is an osteoblast-specific membrane protein that functions in bone mineralization. So far, only two unique pathogenic IFITM5 mutations have been reported: c.119C>T, p.Ser40Leu and the recurrent c.-14C>T. The de novo c.119C>T, p.Ser40Leu mutation was found in one patient diagnosed with bone shortening prenatally and bent bones of the forearms and legs, and unstable hips after birth (Guillén-Navarro et al. 2014). The c.-14C>T mutation was found in more than 90 OI type V cases so far (families or simplex cases) worldwide (Zhang et al. 2012; Cho et al. 2012; Semler et al. 2012, Rauch et al. 2012; Takagi et al. 2013; Shapiro et al. 2013; Rauch et al. 2013; Lazarus et al. 2014). The c.-14C>T variant is predicted to create an in frame alternative start-codon that adds five amino acids to the N-terminus of the wild type IFITM5 protein (Cho et al. 2012; Semler et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

So far, only two pathogenic IFITM5 mutations have been reported (Guillén-Navarro et al. 2014). The clinical sensitivity should be high for patients with clinically diagnosed OI type V. The c.-14C>T IFITM5 mutation was found in almost all clinically diagnosed OI Type V patients tested (Lazarus et al. 2014; Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the IFITM5 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 dominant OI type V, who do not have mutations in the COL1A1 and COL1A2 genes, and the family members of patients who have known IFITM5 mutations.

Gene

Official Gene Symbol OMIM ID
IFITM5 614757
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Osteogenesis imperfecta, type V 610967

Related Tests

Name
Osteogenesis Imperfecta via the BMP1 Gene
Osteogenesis Imperfecta via the CRTAP Gene
Osteogenesis Imperfecta via the FKBP10 Gene
Osteogenesis Imperfecta via the P3H1 / LEPRE1 Gene
Osteogenesis Imperfecta via the SERPINF1 Gene
Osteogenesis Imperfecta via the SERPINH1 Gene
Osteogenesis Imperfecta-Bruck Syndrome Type II via the PLOD2 Gene

Citations

  • Cho T-J, Lee K-E, Lee S-K, Song SJ, Kim KJ, Jeon D, Lee G, Kim H-N, Lee HR, Eom H-H, Lee ZH, Kim O-H, et al. 2012. A Single Recurrent Mutation in the 5?-UTR of IFITM5 Causes Osteogenesis Imperfecta Type V. Am J Hum Genet 91: 343-348. PubMed ID: 22863190
  • 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
  • Guillén-Navarro E, Ballesta-Martínez MJ, Valencia M, Bueno AM, Martinez-Glez V, López-González V, Burnyte B, Utkus A, Lapunzina P, Ruiz-Perez VL. 2014. Two mutations in IFITM5 causing distinct forms of osteogenesis imperfecta. Am. J. Med. Genet 164: 1136-1142. PubMed ID: 24478195
  • Guillén-Navarro E, Ballesta-Martínez MJ, Valencia M, Bueno AM, Martinez-Glez V, López-González V, Burnyte B, Utkus A, Lapunzina P, Ruiz-Perez VL. 2014. Two mutations in IFITM5 causing distinct forms of osteogenesis imperfecta. Am. J. Med. Genet 164: 1136-1142. PubMed ID: 24478195
  • Human Gene Mutation Database (Bio-base).
  • Lazarus S, McInerney-Leo AM, McKenzie FA, Baynam G, Broley S, Cavan BV, Munns CF, Pruijs JEH, Sillence D, Terhal PA, Pryce K, Brown MA, et al. 2014. The IFITM5 mutation c.-14C > T results in an elongated transcript expressed in human bone; and causes varying phenotypic severity of osteogenesis imperfecta type V. BMC Musculoskelet Disord 15: 107. PubMed ID: 24674092
  • Lazarus S, McInerney-Leo AM, McKenzie FA, Baynam G, Broley S, Cavan BV, Munns CF, Pruijs JEH, Sillence D, Terhal PA, Pryce K, Brown MA, et al. 2014. The IFITM5 mutation c.-14C > T results in an elongated transcript expressed in human bone; and causes varying phenotypic severity of osteogenesis imperfecta type V. BMC Musculoskelet Disord 15: 107. PubMed ID: 24674092
  • Rauch F, Glorieux FH. 2004. Osteogenesis imperfecta. Lancet 363: 1377-1385. PubMed ID: 15110498
  • Rauch F, Moffatt P, Cheung M, Roughley P, Lalic L, Lund AM, Ramirez N, Fahiminiya S, Majewski J, Glorieux FH. 2013. Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.−14C>T mutation in all patients. J Med Genet 50: 21-24. PubMed ID: 23240094
  • Semler O, Garbes L, Keupp K, Swan D, Zimmermann K, Becker J, Iden S, Wirth B, Eysel P, Koerber F, Schoenau E, Bohlander SK, et al. 2012. A Mutation in the 5?-UTR of IFITM5 Creates an In-Frame Start Codon and Causes Autosomal-Dominant Osteogenesis Imperfecta Type V with Hyperplastic Callus. Am J Hum Genet 91: 349-357. PubMed ID: 22863195
  • Shapiro JR, Lietman C, Grover M, Lu JT, Nagamani SC, Dawson BC, Baldridge DM, Bainbridge MN, Cohn DH, Blazo M, Roberts TT, Brennen F-S, et al. 2013. Phenotypic Variability of Osteogenesis Imperfecta Type V Caused by an IFITM5 Mutation. J Bone Miner Res 28: 1523-1530. PubMed ID: 23408678
  • Takagi M, Sato S, Hara K, Tani C, Miyazaki O, Nishimura G, Hasegawa T. 2013. A recurrent mutation in the 5′-UTR of IFITM5 causes osteogenesis imperfecta type V. Am. J. Med. Genet. 161: 1980-1982. PubMed ID: 23813632
  • 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
  • Zhang Z, Li M, He J-W, Fu W-Z, Zhang C-Q, Zhang Z-L. 2013. Phenotype and Genotype Analysis of Chinese Patients with Osteogenesis Imperfecta Type V. PLoS ONE 8: e72337. PubMed ID: 23977282

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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