ALPL, BMP1, CREB3L1, CRTAP, FKBP10, P3H1/LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7/OSX, TMEM38B, WNT1
Causative mutations have been identified in thirteen genes associated with autosomal recessive forms of Osteogenesis Imperfecta: FKBP10, CRTAP, P3H1/LEPRE1, PPIB, SERPINH1, SP7/OSX, SERPINF1, PLOD2, ALPL, BMP1, TMEM38B, WNT1 and CREB3L1. The CDL offers a testing panel that sequences these 13 genes simultaneously; this panel is recommended for those individuals with a clear clinical diagnosis of OI who have had normal COL1A1 and COL1A2 gene sequencing studies.
When considering recessive forms of OI, consultation with the laboratory genetic counselors or laboratory director is recommended as clinical and family history and x-ray review may be needed. Occasionally new candidate genes for recessive form of OI will be included as part of the panel; there is no additional charge for testing of these genes.
For guidelines on the correct test to order and for pertinent references, go to OI Guidelines for Diagnostic Testing.
Next Generation Sequencing: DNA was received or extracted from a submitted specimen. Next generation DNA sequencing is performed to identify nucleotide variants in the coding portion of the genome. All nucleotides in the coding exons and their flanking splice junctions are sequenced to a read coverage of greater than 20X. The sequence data are assembled and compared to the published genomic reference sequence. Sanger sequencing is performed if necessary to ensure complete nucleotide coverage of the target sequence and to confirm all reported variants. Human Genome Variation Society (HGVS) recommendations are followed for variant nomenclature and ACMGG/AMP variant interpretation guidelines are followed to assess variant pathogenicity, unless otherwise indicated. The following online databases and in silico analysis tools are routinely used for variant investigation: ClinVar, NHLBI Exome Sequencing Project, 1000 Genomes, dbSNP, Exome Aggregation Consortium (ExAC), available loci specific variant databases, PolyPhen-2, SIFT, Provean, Mutation Taster and Human Splicing Finder.
BLOOD IS PREFERRED.
BLOOD: 2 EDTA (purple top) tubes
Whole blood may be stored up to 5-7 days in the refrigerator before shipping.
Single Gene, +/- array (del/dup):15 µg DNA at a minimum concentration of ≥200 ng/µl
Gene panels, +/- array (del/dup): 35 µg DNA at a minimum concentration of ≥200 ng/µl
Single site (known familial mutation or variant): 5 µg DNA
Oragene Saliva samples are accepted
Amniocytes or Cultured CVS Cells: Two confluent T-25 flasks of cultured amniocytes or CVS cells, well-labeled as Prenatal Sample. Please call ahead to notify the CDL that a prenatal sample will be coming.
Blood samples (or DNA) should be well labeled with patient’s full name and an identifying number.
Ship sample at room temperature with overnight delivery.
Clinical information outlining the indication for the requested tests and pertinent medical history and family history is a necessary component of testing. Please include a clinic note when available.
Radiographs are welcome for analysis by Laboratory Directors.
How to Order
Reflex to Deletion/Duplication Studies: The Collagen Diagnostic Laboratory offers testing for copy number changes using a custom high-density targeted oligonucleotide array for these genes for an additional charge. The targeted regions have probe coverage in both the coding sequences and 10 kb upstream of the gene(s) of interest.
CPT Code & Cost81479