Osteogenesis Imperfecta Core Panel
Test code: MA3401
The Blueprint Genetics Osteogenesis Imperfecta Core Panel is a 11-gene test for genetic diagnostics of patients with clinical suspicion of osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a heritable disease with a prevalence of approximately 6-7:100,000. About 90% of patients have mutations in type I collagen genes (COL1A1 and COL1A2). COL1A1/2-related OI is inherited in an autosomal dominant manner. Several additional genes have been identified and most of the other genes on this panel cause recessively inherited disease. The primary differential diagnosis for individuals with features of COL1A1/2-related OI are autosomal recessive subtypes of OI. The proportion of cases caused by a de novo COL1A1 or COL1A2 mutation varies by the severity of disease: approximately 60% of cases of classic non-deforming OI with blue sclerae or common variable OI with normal sclerae, virtually 100% of perinatally lethal OI, and close to 100% of progressively deforming OI are de novo. Gonadal mosaicism may be present in 3%-5% of cases. Prenatal genetic testing in at-risk pregnancies can be performed if the causative mutation has been identified in an affected relative. This panel is part of the following larger panels: Osteogenesis Imperfecta Panel, Comprehensive Skeletal Dysplasias and Disorders Panel, Skeletal Dysplasia Core Panel and Comprehensive Skeletal / Malformation Syndrome Panel.
About Osteogenesis Imperfecta Core
The OI phenotype is variable, ranging from individuals with a mild predisposition to fractures to lethality in children. Affected individuals with OI type I usually have a relatively mild clinical course and skeletal deformity. They are usually short for their age and have blue/gray sclerae. Many of these individuals experience numerous fractures and dentinogenesis imperfecta is seen in some families. The two mildest forms, classic non-deforming OI and common variable OI, account for considerably more than half of all OI. Severe deforming OI is known as OI types III and IV and characterized by severe deformity of the limbs and marker kyphoscoliosis, thoracic deformity and significant short stature. Typical facial characteristics and wormian bones may be observed and pulmonary function can be diminished because of distortion of the spine and thorax. Severe hearing impairment occurs in 10% of patients. Multiple fractures in the severe OI frequently lead to skeletal deformity. Perinatal lethal OI is also known as OI type II. Approximately 10% of OI patients have this several neonatal form of the disease presenting with severe bone fragility, multiple intrauterine fractures, deformed extremities, and occasianally hydrops fetalis.
Results in 3-4 weeks.
|COL1A2||Ehlers-Danlos syndrome, cardiac valvular form||AD||79||473|
Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.
Blueprint Genetics offers a comprehensive osteogenesis imperfecta core panel that covers classical genes associated with Osteogenesis imperfecta, Bruck syndrome, hypophosphatasia and odontohypophosphatasia. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.
Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.
The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).
Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.
In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.
Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.
A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.
We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.
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Choose an analysis method
ICD & CPT codes
Commonly used ICD-10 codes when ordering the Osteogenesis Imperfecta Core Panel
Accepted sample types
- EDTA blood, min. 1 ml
- Purified DNA, min. 5μg
- Saliva (Oragene DNA OG-500 kit)
Label the sample tube with your patient’s name, date of birth and the date of sample collection.
Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.