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HelpTest Code OIBFG Osteogenesis Imperfecta and Bone Fragility Gene Panel, Varies
Ordering Guidance
Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH/ Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.
Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Additional Testing Requirements
All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen as this must be a different order number than the prenatal specimen.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Necessary Information
Prior Authorization is available, but not required, for this test. If proceeding with the prior authorization process, submit the required form with the specimen.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Prenatal Specimens
Due to its complexity, consultation with the laboratory is required for all prenatal testing; call 800-533-1710 to speak to a genetic counselor.
Specimen Type: Amniotic fluid
Container/Tube: Amniotic fluid container
Specimen Volume: 20 mL
Specimen Stability Information: Refrigerated (preferred)/Ambient
Additional information:
1. A separate culture charge will be assessed under CULAF / Culture for Genetic Testing, Amniotic Fluid.
2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Chorionic villi
Container/Tube: 15-mL tube containing 15 mL of transport media
Specimen Volume: 20 mg
Specimen Stability Information: Refrigerated
Additional Information:
1. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Molecular Testing, Chorionic Villi/Products of Conception.
2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Acceptable:
Specimen Type: Confluent cultured cells
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured cells from another laboratory.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information: All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing (Spanish) (T826)
2. Connective Tissue/Cerebrovascular Disease Genetic Testing Patient Information
4. If not ordering electronically, complete, print, and send a Cardiovascular Test Request (T724) with the specimen.
Secondary ID
617407Useful For
Providing a genetic evaluation for patients with a personal or family history suggestive osteogenesis imperfecta and other hereditary conditions associated with bone fragility
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
| CULAF | Amniotic Fluid Culture/Genetic Test | Yes | No |
| MATCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm
For prenatal specimens only:
-If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture will be added at an additional charge.
-If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture will be added at an additional charge.
For any prenatal specimen that is received, maternal cell contamination testing will be performed at an additional charge.
Special Instructions
- Informed Consent for Genetic Testing
- Informed Consent for Genetic Testing (Spanish)
- Connective Tissue/Cerebrovascular Disease Genetic Testing Patient Information
- Targeted Genes and Methodology Details for Osteogenesis Imperfecta and Bone Fragility Gene Panel
- Osteogenesis Imperfecta and Bone Fragility Gene Panel (OIBFG) Prior Authorization Ordering Instructions
Method Name
Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing
Reporting Name
OI and Bone Fragility Gene PanelSpecimen Type
VariesSpecimen Minimum Volume
Blood: 1 mL; Other specimen types: See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
Osteogenesis imperfecta (OI) is a hereditary skeletal dysplasia syndrome characterized primarily by bone fragility and skeletal deformities, with other possible features including dental abnormalities, hearing loss, and blue/gray sclera.(1,2) Historically, OI was classified into  subtypes based on clinical presentation only: nondeforming with persistently blue sclera (OI type I), perinatal lethal (OI type II), progressively deforming (OI type III), moderate (OI type IV), and with calcification of the interosseous membranes and/or hypertrophic callus (OI type V). While these clinical classifications are still commonly used, it is recommended that OI subtypes are classified by genetic etiology.(3) Currently, there are approximately 20 different genetic subtypes of OI with variable modes of inheritance and pathophysiology.(1-3)
The most common genetic etiology of OI is disease-causing variants in the COL1A1 and COL1A2 genes encoding the pro alpha 1(I) and pro alpha 2(I) chains of type I procollagen, respectively. It is estimated that up to 25% of cases of OI are caused by disease-causing variants in either COL1A1 or COL1A2.(1-3) Disease-causing variants in these genes result in the inability to properly synthesize the pro alpha 1/2 molecules ultimately leading to abnormal or absent collagen I, a critical molecule for the structural integrity of bone. COL1A1/2-associated OI is inherited in an autosomal dominant manner and can result in a spectrum of disease severity, classified into OI types I-IV.(3)
Other genetic etiologies of OI are associated with genes involved in bone mineralization, collagen modification, collagen processing, collagen cross-linking, and osteoblast differentiation and function.(3) The majority of these less common genetic OI subtypes are inherited in an autosomal recessive manner, with the exception of autosomal dominant IFITM5-associated OI (also known as OI type V), and X-linked recessive MBTPS2-associated OI (also known as OI type XVII).
Several genetic conditions leading to bone fragility have significant overlap with OI. Additional conditions covered by this panel include ALPL-associated hypophosphatasia, ANO5-associated gnathodiaphyseal dysplasia, FKBP10-associated Bruck syndrome, LRP5-associated osteoporosis, P4HB-associated Cole-Carpenter syndrome, PLOD2-associated Bruck syndrome, PLS3-associated X-linked osteoporosis, TAPT1-associated osteochondrodysplasia, and XYLT2-associated spondyloocular syndrome with bone fragility, cataracts and hearing defects.
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(4) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Method Description
Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.
There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Osteogenesis Imperfecta and Bone Fragility Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)
Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.
Genes analyzed: ALPL, ANO5, BMP1, COL1A1, COL1A2, CREB3L1, CRTAP, FKBP10, IFITM5, LRP5, MBTPS2, P3H1, P4HB, PLOD2, PLS3, PPIB, SEC24D, SERPINF1, SERPINH1, SP7, SPARC, TAPT1, TMEM38B, WNT1, and XYLT2
Day(s) Performed
Varies
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81406 x2
81408 x2
81479
81479 (if appropriate for government payers)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| OIBFG | OI and Bone Fragility Gene Panel | 51966-0 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 617408 | Test Description | 62364-5 |
| 617409 | Specimen | 31208-2 |
| 617410 | Source | 31208-2 |
| 617411 | Result Summary | 50397-9 |
| 617412 | Result | 82939-0 |
| 617413 | Interpretation | 69047-9 |
| 617414 | Additional Results | 82939-0 |
| 617415 | Resources | 99622-3 |
| 617416 | Additional Information | 48767-8 |
| 617417 | Method | 85069-3 |
| 617418 | Genes Analyzed | 48018-6 |
| 617419 | Disclaimer | 62364-5 |
| 617420 | Released By | 18771-6 |
Prior Authorization
Insurance preauthorization is available for this testing; forms are available.
Patient financial assistance may be available to those who qualify. Patients who receive a bill from Mayo Clinic Laboratories will receive information on eligibility and how to apply.