It is now clear that missense and synonymous variants within exons and some intronic variants can affect pre-mRNA splicing. While predictive programs can identify alterations in splice enhancers and suppressors and creation or deletion of recognition sequences, they are poor at determining if they are used. Additionally, it is difficult to determine the splice outcomes of variants identified by genomic sequencing. The CDL now offers mRNA splicing studies of genes that are included in our test menu and are expressed in dermal fibroblasts.
The Collagen Diagnostic Laboratory is pleased to announce new testing for Stickler syndrome, a connective tissue disorder involving collagen types II, IX, and XII. The CDL offers a 6 gene panel to test for Stickler syndrome. Please see the Stickler Syndrome Test Page for more information.
The billing portion of the CDL and NCGL laboratory test requisition forms has been revised to include patient consent when billing insurance. A patient signature is now required for all insurance billing. Additional security features have also been added to protect credit card information. Please see the CDL Billing Page or NCGL Billing Page for details!
Solid tumors (e.g. sarcomas, lung cancers, thyroid cancers, head and neck cancers, renal cell carcinomas, mammary gland tumors, prostate cancers, brain tumors) frequently have chromosome rearrangements and gene fusions that are important in establishing a diagnosis, predicting prognosis, and guiding therapy choices. The CCL now offers Archer’s FusionPlex Panel, which is based on next generation sequencing of RNA (cDNA) from solid tumor tissue to detect somatic oncogenic gene fusions involving any of 100 genes associated with solid tumors, without prior knowledge of the fusion partners or the breakpoints of the translocations. More details can be found HERE.
The Clinical Cytogenomics Lab now offers droplet digital PCR as a test option. ddPCR is a less expensive way of testing family members for small genomic deletions and duplications that were first detected by cytogenomic SNP microarray. ddPCR also offers a way to do targeted testing for the deletion or duplication of interest. This avoids the possibility of incidental findings. More details can be found HERE.
Yajuan J. Liu, PhD, director of the Center For Precision Diagnostics’ Clinical Cytogenomics Laboratory, is the last author on a paper recently published in Cancer Genetics: “High amplification levels of MDM2 and CDK4 correlate with poor outcome in patients with dedifferentiated liposarcoma: A cytogenomic microarray analysis of 47 cases.” The work was done in collaboration with colleagues in the University of Washington Departments of BioStatistics and Laboratory Medicine, Anderson Cancer Center, Prevention Genetics, and Hebei University (China). The goal was to use cytogenomic microarray analysis (CMA) to identify genomic abnormalities that correlate with survival, as a way to stratify the risk faced by people diagnosed with dedifferentiated liposarcomas (DDLS). Forty-seven patients with DDLS were identified, and CMA was performed on archived tumor samples. Liu and colleagues found that increased copy number of the MDM2 and CDK4 genes is strongly correlated with decreased survival (poorer prognosis). They also saw a synergistic effect, in that amplification of one of these genes increases the poor prognostic effect that each additional copy of the other gene has. Increased copy number for the JUN gene may also be correlated with poorer prognosis.
The CDL is pleased to announce the addition of five new NextGen panels, including our most comprehensive panel for Osteogenesis Imperfecta to date, the 30-gene OI and Genetic Bone Disorders Panel. The CDL offers new testing for Osteopetrosis, Cutis Laxa, Ectopia lentis, and Complex EDS-like Disorders. As always, the CDL is committed to providing the most comprehensive analysis, interpretation and follow-up of these genes and all genes involved in inherited disorders of connective tissue.
Dr. Peter Byers, Director of the UW Medicine Center for Precision Diagnostics, will be presenting at the upcoming ACMG Annual Clinical Genetics Meeting in Phoenix, Arizona.
Topic: What Every Clinical Geneticist Should Know About Testing for Osteogenesis Imperfecta in Suspected Child Abuse Cases
Date: Friday, March 24, 2017
Time: 1:40 PM – 2:00 PM
Location: Phoenix Convention Center
Room: North Ballroom BC
For more information, please visit the conference page HERE
Each year in the UW some 25,000 children between the ages of birth and 3years are abused in ways that result in fractures. In that same age group are about 1200 infants and children with osteogenesis imperfecta (OI) and a smaller number with other genetic predispositions to bone fragility and fracture. The presentation of fracture in children with OI may mimic that of children who have been abused in that multiple unexplained fractures can be present and baffle both the parents and the clinicians as to their origin. More than 90% of individuals with OI have mutations in the type I collagen genes (COL1A1 and COL1A2) and all but a handful of the rest have mutations in any of an additional 15 genes. Mutations in all these genes can now be reliably identified by genetic sequence analysis, which has completely supplanted analysis of proteins produced by cultured fibroblasts for diagnosis. The decision of which children to study in the context of concerns about abuse is difficult and even the most stringent procedures to screen out children with OI still leaves questions in a small number among whom about 5% have genetic and biochemical evidence of OI upon testing. In that context the failure to find a causative genetic alteration, .however, dramatically lowers the likelihood that a child has OI and facilitates further assessment of the family.
The Center for Precision Diagnostics, Collagen Diagnostic Laboratory is pleased to announce that genetic testing for Ehlers-Danlos syndrome (EDS) periodontal type is now available individually and through our new Comprehensive EDS Panel. The testing for EDS periodontal type (also known as EDS type VIII) includes genomic sequence analysis of C1S and C1R. Researchers in our group recently described pathogenic variants in these two genes as the underlying cause of EDS VIII. This autosomal dominant disorder is characterized by early-onset periodontitis and tooth loss.
The Center for Precision Diagnostics researchers, in collaboration with Austrian, Swedish and UK geneticists, recently identified that the cause of the periodontal form of Ehlers-Danlos syndrome (EDS type VIII) results from a mutation in one of an unexpected pair of genes, C1S or C1R. Both genes dictate the synthesis of complement, a protein that plays a role in fighting infection and moving foreign cells out the cell. Most other forms of EDS are caused by sequence variants in collagen proteins. A C1S or C1R gene sequence abnormality leads to a dominant form of EDS type VIII , causing aggressive periodontitis and tooth loss at a young age. The surprising discovery accomplished by exome sequencing research is opening the door to learn how the disease progresses, a necessary step for considering treatment. Read the details of the research in the American Journal of Human Genetics.
The CPDx recognizes that obtaining insurance pre-authorization for genetic testing may be challenging and time consuming. We are happy to assist clients in obtaining prior authorizations to determine whether genetic testing will be a covered service under the patient’s plan.
Center for Precision Diagnostics laboratory director, Dr. Peter Byers and genetic counselor, Melanie Pepin recently attended the Ehlers-Danlos Society (EDS) International Symposium 2016 in New York City (May 3-6, 2016). Invited members of the EDS medical community and interested affected individuals and family members from around the world gathered to update and expand present clinical diagnostic categories and nomenclature for the many forms of EDS. Both Dr. Byers and Melanie presented clinical data gathered from research participants in the Collagen Diagnostic Research Repository.