Test Catalog

Test Id : OIBFG

Osteogenesis Imperfecta and Bone Fragility Gene Panel, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Providing a genetic evaluation for patients with a personal or family history suggestive osteogenesis imperfecta and other hereditary conditions associated with bone fragility

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 25 genes associated with osteogenesis imperfecta (OI) and other hereditary conditions associated with bone fragility: 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. See Targeted Genes and Methodology Details for Osteogenesis Imperfecta and Bone Fragility Gene Panel and Method Description for additional details.

 

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for OI and other hereditary conditions associated with bone fragility.

 

Prior Authorization is available for this assay.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
_STR1 Comp Analysis using STR (Bill only) No, (Bill only) No
_STR2 Add'l comp analysis w/STR (Bill Only) No, (Bill only) No
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
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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.

Method Name
A short description of the method used to perform the test

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

OI and Bone Fragility Gene Panel

Aliases
Lists additional common names for a test, as an aid in searching

Bone fragility

Brittle bone disease

Bruck syndrome

Cole-Carpenter syndrome

Gnathodiaphyseal dysplasia

Hypophosphatasia

NextGen Sequencing Test

OI

OI type I

OI type II

OI type III

OI type IV

OI type V

OI type VI

OI type VII

OI type VIII

OI type IX

OI type X

OI type XI

OI type XII

OI type XIII

OI type XIV

OI type XV

OI type XVI

OI type XVII

OI type XIX

Osteochondrodysplasia

Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type

Osteogenesis imperfecta

Osteoporosis

Osteoporosis pseudoglioma syndrome

Spondyloocular syndrome

X-linked osteoporosis

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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.

Specimen Type
Describes the specimen type validated for testing

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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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

3. Osteogenesis Imperfecta and Bone Fragility Gene Panel (OIBFG) Prior Authorization Ordering Instructions

4. If not ordering electronically, complete, print, and send a Cardiovascular Test Request (T724) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 1 mL; Other specimen types: See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Providing a genetic evaluation for patients with a personal or family history suggestive osteogenesis imperfecta and other hereditary conditions associated with bone fragility

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 25 genes associated with osteogenesis imperfecta (OI) and other hereditary conditions associated with bone fragility: 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. See Targeted Genes and Methodology Details for Osteogenesis Imperfecta and Bone Fragility Gene Panel and Method Description for additional details.

 

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for OI and other hereditary conditions associated with bone fragility.

 

Prior Authorization is available for this assay.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

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.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variants in an affected family member would allow for more informative testing of at-risk individuals.

 

To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact the Mayo Clinic Laboratories genetic counselors at 800-533-1710.

 

Technical Limitations:

Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

 

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. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

 

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.

 

Deletion/Duplication Analysis:

This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

 

This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

Genes may be added or removed based on updated clinical relevance. Refer to the Targeted Genes and Methodology Details for Osteogenesis Imperfecta and Bone Fragility Gene Panel for the most up to date list of genes included in this test. For detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor.

 

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

Reclassification of Variants:

At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages healthcare providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time.

 

Variant Evaluation:

Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(4) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

 

Rarely, incidental or secondary findings may implicate another predisposition or presence of active disease. Incidental findings may include, but are not limited to, results related to the sex chromosomes. These findings will be carefully reviewed to determine whether they will be reported.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Marom R, Rabenhorst BM, Morello R: Osteogenesis imperfecta: an update on clinical features and therapies. Eur J Endocrinol. 2020 Oct;183(4):R95-R106. doi:10.1530/EJE-20-0299

2. Steiner RD, Basel D: COL1A1/2 osteogenesis imperfecta. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2005. Updated May 6, 2021. Accessed August 1, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1295/

3. Marini JC, Forlino A, Bachinger HP, et al: Osteogenesis imperfecta. Nat Rev Dis Primers. 2017 Aug 18;3:17052. doi: 10.1038/nrdp.2017.52

4. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424

Method Description
Describes how the test is performed and provides a method-specific reference

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

 

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

Supplemental

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

28 to 42 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole blood: 2 weeks (if available); Extracted DNA: 3 months; Cord blood, amniotic fluid, cultured amniocytes, chorionic villi, cultured chorionic villi: 1 month

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81406 x 2

81408 x 2

81479

81479 (if appropriate for government payers)

88233-Tissue culture, skin, solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

88235-Amniotic fluid culture (if appropriate)

81265-Maternal cell contamination (if appropriate)

Prior Authorization
Prior Authorization may be required by your insurance carrier.

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.

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

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
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
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 In Process
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

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | PHP Pdf | CMS Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports