Osteogenesis Imperfecta Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: MA3001

The Blueprint Genetics Osteogenesis Imperfecta Panel is a 61 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 recently been identified. Mutations in all of the recently identified genes (except IFITM5 which causes OI type V) cause recessively inherited OI. 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 Comprehensive Skeletal / Malformation Syndrome panel.

About Osteogenesis Imperfecta

The OI phenotype is variable, ranging from osteoporosis presenting in adulthood to lethality in children. The two mildest forms, classic non-deforming OI and common variable OI, account for considerably more than half of all OI. The major clinical manifestation is skeletal fragility. Skeletal deformity, joint laxity, and scoliosis may be present. Other extraskeletal manifestations include hearing loss, dentinogenesis imperfecta, blue/gray sclerae, hypercalciuria, aortic root dilatation, and neurologic conditions such as macrocephaly, hydrocephalus, and basilar invagination. Even adults with “mild” OI may have significant musculoskeletal symptoms, including arthritis, fractures, back pain, scoliosis, and tendon ruptures.


Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more.

Genes in the Osteogenesis Imperfecta Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ALPLOdontohypophosphatasia, Hypophosphatasia perinatal lethal, infantile, juvenile and adult formsAD/AR32270
ANO5Gnathodiaphyseal dysplasia, LGMD2L and distal MMD3 muscular dystrophiesAR42106
ATP6V0A2Cutis laxa, Wrinkly skin syndromeAR1652
B3GALNT2Muscular dystrophy-dystroglycanopathyAR713
B4GALT7Ehlers-Danlos syndrome, progeroid formAR88
BMP1Osteogenesis imperfectaAR611
CAPN3Muscular dystrophy, limb-girdle, Eosinophilic myositisAR102400
CFL2Nemaline myopathyAR23
CHKBMuscular dystrophy, congenital, megaconialAR522
CLCN5Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, Hypophosphatemic rickets,, Nephrolithiasis, I, Dent diseaseXL37255
COL1A1Ehlers-Danlos syndrome, Caffey disease, Osteogenesis imperfecta type 1, Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4AD120883
COL1A2Ehlers-Danlos syndrome, cardiac valvular form, Osteogenesis imperfecta type 1, Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4AD79473
COL6A1Bethlem myopathy, Ullrich congenital muscular dystrophyAD/AR4695
COL6A2Epilepsy, progressive myoclonic, Bethlem myopathy, Myosclerosis, congenital, Ullrich congenital muscular dystrophyAD/AR65134
COL6A3Bethlem myopathy, Dystonia, Ullrich congenital muscular dystrophyAD/AR36105
CRTAPOsteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4AR1124
DNM2Myopathy, Lethal akinesia and musculoskeletal abnormalities, with brain and retinal hemorrhages, Charcot-Marie-Tooth diseaseAD/AR2344
EMDEmery-Dreifuss muscular dystrophyXL28111
ENPP1Arterial calcification, Hypophosphatemic ricketsAR1772
FGF23Tumoral calcinosis, hyperphosphatemic, Hypophosphatemic ricketsAD/AR716
FHL1*Myopathy with postural muscle atrophy, Emery-Dreifuss muscular dystrophy, Reducing bod myopathyXL1847
FKBP10Bruck syndrome type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4AR1727
FKRPMuscular dystrophy-dystroglycanopathyAR3199
FKTNMuscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle)AD/AR2851
FLNAFrontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defectsXL86209
FLNBLarsen syndrome (dominant), Atelosteogenesis type 1, Atelosteogenesis type 3, Spondylo-carpal-tarsal dyspasiaAD/AR3898
GAAGlycogen storage diseaseAR79503
GMPPBMuscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), Limb-girdle muscular dystrophy-dystroglycanopathyAR1326
ISPDMuscular dystrophy-dystroglycanopathyAR2042
KBTBD13Nemaline myopathyAD36
KLHL40Nemaline myopathyAR524
LAMA2Muscular dystrophy, congenital merosin-deficient, SchizophreniaAD/AR72225
LAMP2Danon diseaseXL4681
LARGEMuscular dystrophy-dystroglycanopathyAR1522
LMNAHeart-hand syndrome, Slovenian, Limb-girdle muscular dystrophy, Muscular dystrophy, congenital, LMNA-related, Lipodystrophy (Dunnigan), Emery-Dreiffus muscular dystrophy, Malouf syndrome, Dilated cardiomyopathy (DCM), Mandibuloacral dysplasia type A, Progeria Hutchinson-Gilford typeAD/AR183458
LRP5*Van Buchem disease, Osteoporosis-pseudoglioma syndrome, Hyperostosis, endosteal, Osteosclerosis, Exudative vitreoretinopathy, Osteopetrosis late-onset form type 1, LRP5 primary osteoporosisAD/AR/Digenic36163
MYH7Hypertrophic cardiomyopathy (HCM), Myopathy, myosin storage, Myopathy, distal, Dilated cardiomyopathy (DCM)AD/AR285748
NEB*Nemaline myopathyAR34262
OCRLLowe syndrome, Dent diseaseXL33251
P3H1Osteogenesis imperfectaAR1233
PHEXHypophosphatemic ricketsXL75411
PIEZO2*Marden-Walker syndrome, Distal arthrogryposisAD2124
PLOD2Bruck syndrome, Osteogenesis imperfecta type 3AR411
POMGNT1Muscular dystrophy-dystroglycanopathyAR5573
POMT1Muscular dystrophy-dystroglycanopathyAR3181
POMT2Muscular dystrophy-dystroglycanopathyAR2848
PPIBOsteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4AR611
PYCR1Cutis laxa AR type 2BAR1234
RAPSNMyasthenic syndrome, congenitalAR1857
RYR1Central core disease, Malignant hyperthermia, Minicore myopathy with external ophthalmoplegia, Centronuclear myopathy, Minicore myopathy, Multicore myopathyAD/AR123563
SELENONMuscular dystrophy, rigid spine, Myopathy, congenital, with fiber- disproportionAR1650
SERPINF1Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4AR729
SERPINH1Osteogenesis imperfecta type 3AR35
SIL1Marinesco-Sjogren syndromeAR1449
SLC34A3Hypophosphatemic rickets with hypercalciuriaAR1036
TMEM5Muscular dystrophy-dystroglycanopathyAR87
TMEM43Arrhythmogenic right ventricular dysplasia, Emery-Dreifuss muscular dystrophyAD515
TNNT1Nemaline myopathyAR25
TPM2CAP myopathy, Nemaline myopathy, Arthrogryposis, distalAD1137
TPM3*CAP myopathy, Nemaline myopathy, Myopathy, congenital, with fiber- disproportionAD1826
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

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 panel that covers classical genes associated with osteogenesis imperfecta. 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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ICD & CPT codes

CPT codes


ICD codes

Commonly used ICD-10 codes when ordering the Osteogenesis Imperfecta Panel

Q78.0Osteogenesis imperfecta

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.