Osteogenesis Imperfecta via the IFITM5 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
1657 IFITM5$440.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

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).

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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).
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).
Testing Strategy
The IFTIM5 protein is coded by exons 1 to 2 of the IFTIM5 gene on chromosome 11p15.5. Targeted testing for the c.-14C>T variant will be performed first, and if the patient is negative for this variant, then the rest of the gene will be tested. Testing involves PCR amplification from genomic DNA and bidirectional Sanger sequencing of the coding exons and ~10bp of adjacent noncoding sequences. We will also sequence any single exon (Test #100) in family members of patients with a known mutation or to confirm research results.
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.


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


Name Inheritance OMIM ID
Osteogenesis imperfecta, type V 610967

Related Tests

Osteogenesis Imperfecta via BMP1 Gene Sequencing with CNV Detection
Osteogenesis Imperfecta via CRTAP Gene Sequencing with CNV Detection
Osteogenesis Imperfecta via FKBP10 Gene Sequencing with CNV Detection
Osteogenesis Imperfecta via P3H1 / LEPRE1 Gene Sequencing with CNV Detection
Osteogenesis Imperfecta via SERPINF1 Gene Sequencing with CNV Detection
Osteogenesis Imperfecta via SERPINH1 Gene Sequencing with CNV Detection
Osteogenesis Imperfecta via the COL1A1 Gene
Osteogenesis Imperfecta via the COL1A2 Gene
Osteogenesis Imperfecta-Bruck Syndrome Type II via the PLOD2 Gene


Genetic Counselors
  • 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
  • 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
  • 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
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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