Large Cryptic Derivative Chromosome 8 Detected by SNP Chromosomal Microarray

s 365 Large Cryptic Derivative Chromosome 8 Detected by SNP Chromosomal Microarray Heather Jacques , Karen Swisshelm , Susan Toomey , Billie Carstens , Jamie LeRoux , Matthew Taylor , Darcy Huismann b Colorado Genetics Laboratory, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; University of Colorado Hospital, Aurora, CO, USA We present a case of a 33-year-old female referred for intellectual disability, dysmorphic features, and a family history of intellectual disability. A CytoSNP-850K bead microarray, along with focused cytogenetic analysis, revealed a derivative chromosome with a 9.3 Mb gain of 2p25.3-p25.1 and a 8.8 Mb loss of 8p23.2-p23.1 material. These 2 copy number variants are located in the terminal regions of these chromosomes and contain over 80 genes, including 8 OMIM genes. While partial trisomy 2p is quite rare, 8p deletions are widely reported in literature. Clinical features of these copy number variants include variable intellectual deficits, dysmorphic facial features, growth retardation, behavior issues and developmental delay. The banding patterns of the chromosomes involved, and the particular locations of the gain and loss of genomic material, contribute to the cryptic nature of this derivative chromosome. Prior highresolution studies utilizing G-banding did not detect this abnormality and a 46,XX normal karyotype was initially reported. Chromosomal microarray was a necessary tool for proper diagnosis for this individual and the family. Further familial studies are needed, but this derivative is likely the result of a balanced, cryptic, familial translocation, as other family members are also affected. This case demonstrates how chromosomal microarray, combined with traditional cytogenetics, is a productive approach for identifying large, yet cryptic, structural abnormalities. Streamlining NGS Workflows Using Cancer Samples by the Application of Tthe DNA Integrity Number (DIN) from the Genomic DNA Screentape Assay Solange Borg , Isabell Pechtl , Barry McHoull , Eva Schmidt b Agilent Technologies, La Jolla, CA, USA; Agilent Technologies, Waldbronn, Germany; Agilent Technologies UK Limited, Edinburgh, UK The results of numerous molecular screening and assay methods often rely on the overall quality of the genomic DNA (gDNA) input material. However, extraction of genetic material can be challenging and often results in low amounts or variable quality of gDNA samples, which are further subjected to time and cost intensive downstream applications. For example, array comparative genome hybridization (aCGH) and next generation sequencing (NGS) can require intact, high-quality gDNA to ensure high-quality, unambiguous results. It is therefore widely recommended to perform an initial quality control (QC) of the input material. Especially as only the final step of these workflows reveals if meaningful results have been achieved. In order to provide an objective and automated measure to standardize the gDNA integrity assessment, a software algorithm has been developed. This functionality of the 2200 TapeStation system provides a numerical determination of the gDNA integrity and is referred to as the DNA Integrity Number (DIN). This study demonstrates how DIN obtained by the upfront QC of gDNA on the Agilent Genomic DNA ScreenTape assay has allowed for significant saving of sequencing and sample preparation overhead using cancer samples in NGS workflows. Conflict of Interest: All authors are full-time employees of Agilent Technologies. Bilateral Radial Ray Defects: An Atypical Presentation of 16p11.2 Microdeletion Syndrome Stephanie E. Vallee , Laura J. Tafe , Elizabeth Reader , Mary Beth P. Dinulos , Liming Bao , Gregory J. Tsongalis , Joel A. Lefferts b Department of Pediatrics, Section of Medical Genetics, Lebanon, NH, USA; Department of Pathology, Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, NH, USA Advances in microarray technology have allowed for identification of a recurring microdeletion syndrome involving chromosome region 16p11.2. This contiguous gene deletion syndrome includes the TBX6 (T-BOX 6) gene and is primarily characterized by neurodevelopmental disorders. Congenital malformations are occasionally reported and primarily include heart defects such as aortic valve abnormalities and patent foramen ovale. We report a newborn male with multiple congenital anomalies including upper extremity radial ray defects, large ventricular septal defect, moderate secundum atrial septal defect, asymmetric number of ribs and abnormally shaped scapulae. Radiographs confirmed absence of the right radius, bowed right ulna, and bilateral thumb hypoplasia. Physical examination was significant only for anomalies of the upper extremities with no additional dysmorphic features. Microarray analysis detected a 751 kb deletion from cytoband 16p11.2. Though slightly larger than the typical 593 kb deletion, only 1 OMIM gene is within this distal region. Review of the medical literature identified 1 prior case report with suspected radial ray defects in an individual with 16p11.2 microdeletion syndrome. In that case, the infant presented with left-sided congenital diaphragmatic hernia, lethal respiratory distress and was noted to have hypoplastic non-articulating thumbs, extrathoracic vertebra, and 13 pairs of ribs (Wat et al, 2011; PubMed: 21525063). The TBX6 gene, which encodes a transcription factor, plays a critical role in important developmental processes including paraxial mesoderm differentiation and lefteright patterning. Loss of TBX6 has been suggested as a contributing factor for congenital anomalies associated with 16p11.2. This case expands the phenotypic spectrum of 16p11.2 microdeletion syndrome.