• Test Code:
  • Department:
  • Test Synonyms:
    COL1A1COL1A2 IFITM5LRP5Brittle bone diseaseFragilitas ossiumOIVrolik disease
  • CPT Code(s):

Osteogenesis Imperfecta (OI) is a group of disorders that affect bone fragility and formation. OI is characterized by fractures with minimal or absent trauma, short stature, blue sclera, and dentinogenesis imperfecta. There are 19 known types of this disorder with a wide range of features and severities. A majority of patients with OI have a mutation in either the COL1A1 or COL1A2 gene, which are the genes that code for alpha 1 and alpha 2 chains of collagen type I.  Mutations in COL1A1 and COL1A2 are associated with autosomal dominant inheritance, and can present with a wide phenotypic spectrum from perinatal lethality to mild predisposition to fractures.

Another autosomal dominant form of OI is caused by mutations in IFITM5. Mutations in this gene are associated with OI type V, which also has a wide phenotypic range, but does have distinct clinical and radiological features. Autosomal recessive OI is less common.

Combining exon – level deletion/duplication data analyzed by microarray with sequence analysis by next generation sequencing data will allow KDL to improve diagnostic yield and deliver more comprehensive results.

The results from genetic tests can facilitate assessment of levels of risk for patients and lead to more efficient and appropriate medical management. It is recommended that this testing be accompanied by a complete family history and genetic counseling.

Reasons for Referral:

  • Molecular confirmation of a clinical diagnosis of Osteogenesis Imperfecta.
  • To aid in decision-making for treatment and management of individuals with Osteogenesis Imperfecta.
  • Testing for individuals with a positive family history for Osteogenesis Imperfecta (targeted testing is available if the familial mutation is known).


Next generation sequencing (NGS) will analyze the exons or coding regions of three Autosomal Dominant Osteogenesis Imperfecta-associated genes using Illumina NextSeq 500/550 technology.  Samples are prepared using hybridization probes to enrich exonic regions.  This assay does not assess regions of insufficient coverage, introns and promoter regions; pseudogenes; where the reference genome is inaccurate or contains gaps and insertions; and regions of high GC or polynucleotide repeats, but may contain variants that impact gene function.

Exon-level deletion/duplication analysis is performed by running the NGS data through the Genome Analysis Toolkit (GATK) Germline Copy Number Variation best practices pipeline from GATK, version A Bayesian model was validated clinically in our lab. The model can detect copy changes at a resolution of three (3) or more probe targets (exons) for deletions and duplications in genes that do not have pseudogenes, and is not designed to detect low-level mosaicism or balanced alterations. 

The four Autosomal Dominant Osteogenesis Imperfecta-associated genes are listed below:

Specimen Requirements:

Blood: EDTA or ACD (Solution A or B):

  • Adult: 5 mL
  • Child: 5 mL
  • Infant: 2-3 mL

Saliva: 2 ORAgene™ Saliva Collection Kit(s) (OGR-500) used according to manufacturer instructions. Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.

Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions.  Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.

Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks


  • Direct Amniotic Fluid (10-20mL)
  • Direct CVS
  • Cultured Amniocytes (2-T25 flasks)
  • Cultured CVS (2-T25 flasks)
  • Cultured Fetal Tissue: Product of Conception (2-T25 flasks)
  • Cord Blood (1-2-mL)

DNA: 5-10µg at a minimum of 60-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

  • Maternal cell rule-out testing will be performed on all prenatal specimens received. Please provide maternal blood in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test.
  • All genetic testing performed on Direct CVS or Amniotic Fluid specimens will be confirmed on cell cultures prepared by Knight Diagnostic Laboratories. Cell cultures will be prepared from the specimen received. Additional charges apply for confirmatory testing.

For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):


Turn Around Time:

8 weeks

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.


  1. Genetics Home Reference https://ghr.nlm.nih.gov/condition/osteogenesis-imperfecta 
  2. Uncommon IFITM5 mutation associated with severe skeletal deformity in osteogenesis imperfecta. Rodriguez Celin M1, Moosa S2, Fano V1. https://www.ncbi.nlm.nih.gov/pubmed/30039845 
  3. Genotype-Phenotype Correlations in Autosomal Dominant Osteogenesis Imperfecta Mouna Ben Amor, Francis H. Glorieux, and Frank Rauch  Shriners Hospital for Children and McGill University, Montreal, QC, Canada https://doi.org/10.4061/2011/540178 

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

Learn More