Day 2 :
CDH International, USA
Time : 09:30-10:15 AM
Dawn M Ireland is the Founder of CHERUBS - The Association of Congenital Diaphragmatic Hernia Research, Awareness and Support. She stepped away as President of CHERUBS and into the role of President of CDH International to further the research projects that the organization is involved in. Currently, she oversees CDH International which now runs the world’s largest natural history database of CDH which has 3 boards, employees, many volunteers, assists over 6300 patient families in 70 countries, presents research abstracts and works with both the NIH and the EU. She is also a Founding Member of the Rare Advocacy Movement and senior level patient advocate, mentors several other non-profit organizations, Founding Member of the Alliance of Congenital Diaphragmatic Hernia Organizations, written/edited 4 books and spends her time between the United States and Europe to continue the organization’s growth and outreach.
Purpose: Our objective was to assess the amount of medical information retained by parents of children born with Congenital Diaphragmatic Hernia. Our goal is to review the difference in our study with the population studies of other CDH research groups such as the CDH Study Group and DHREAMS in the amount of information given and correctly retained by CDH parents.
Methods: We reviewed the answers provided to a questionnaire between 1995 and 2014. Members included 2547 survivors, 1294 non-survivors and 740 expectant or who did not follow up. Parents were asked basic medical questions as well as a detailed medical and familial history.
Results: Our questionnaire was answered by 4548 families. A higher percentage of families of non-surviving infants than surviving infants did not know if their child's CDH occurred on the left versus right side (46.8% vs. 57.8%). When families were asked to further characterize the type of decent their child had, the percentage of those who did not know jumped to approximately 87%, showing that even fewer parents remembered the finer details of their child's diagnosis. Familial CDH is reported in the literature to be known in approximately 2% of all cases. Our membership reports 1.6%, which is similar to what has been reported.
Conclusion: Until this study is compared to the studies of DHREAMS and the CDH Study Group and exact patient matching occurs, it is difficult to measure the true medical knowledge that CDH parents grasp and remember.
Sonic Healthcare, Australia
Time : 10:15-11:00 AM
Dr Michael J Sinosich established the Division of Prenatal Testing within Sonic Clinical Institute in 2002. Michael is an internationally respected investigator in early pregnancy well-being. He has published extensively in peer reviewed journals and presented numerous papers at local, national and international forums.
The urge to procreate has spawned IVF-ART industry and similarly, the desire to know (prenatally) the wellbeing of your unborn child has generated prenatal diagnostic services. Non-Invasive Prenatal Screening (NIPS) includes proteomic, molecular and ultrasonographic testing modalities, applied prenatally to identify a subset of obstetric population assessed to be at increased risk for disorder being screened. Through recent technical advances, quantitation of low abundance DNA has enabled non-invasive prenatal fetal chromosome enumeration. Screening for feto-placental wellbeing, includes ALL current screening modalities: Proteomic (PAPP-A, FbhCG, AFP, PlGF), ultrasonography (NT), extracellular (cf) and intracellular (genomic) DNA. Prior to any definitive intervention, patients with positive screening result should be counseled to seek confirmatory diagnostic testing. Combination of feto-placental biochemistry with ultrasonographic biometry can provide Trisomy 21 detection rate of 92.9%. Whilst not matching performance of cfDNA (DR=99.9%), clinical application of combine first trimester biochemistry extends beyond screening just for Trisomy 21. Fetal triploidy, which is undetectable by many cfDNA algorithms, presents with median Nuchal Translucency (NT) of 1.35 mm. However, median PAPP-A (0.06 MoM) and FbhCG (0.24 MoM) clearly signal a clinical situation warranting further investigation. Inclusion of PlGF has introduced another dimension to screening because now we can simultaneously screen for fetal and maternal wellbeing, such as, pre-eclampsia. Recent developments allow isolation of fetal-placental cells, which can be applied for chromosome enumeration and for Whole Genome Sequencing (WGS). Cellular targets include Nucleated Fetal Red Blood Cells (NFRBC), Mononucleated Cytotrophoblast (CT) and Polynucleated Syncytiotrophobslast (SCT) cells. After initial enrichment, fetal cell isolation is achieved by laser dissection. Whilst providing a pure fetal cell, this technology is labor intensive and hence, not yet applicable to population based screening. Over the past two decades, non-invasive prenatal screening has progressed from screening for targeted fetal abnormalities to combined prenatal assessment of feto-maternal wellbeing and finally, to prenatal fetal whole genome sequencing.
Xi’an Jiaotong University, China
Time : 11:15 AM- 12:00 PM
Kai Ye has completed his PhD from Leiden University in the Netherlands and Postdoctoral studies from European Bioinformatics Institute in UK. He has worked as an Assistant Professor at Leiden University Medical Center and Washington University in St. Louis. He has published more than 50 papers in reputed journals.
Complex insertions and deletions (indels) are formed by simultaneously deleting and inserting DNA fragments of different sizes at a common genomic location. Here we present a systematic analysis of somatic complex indels in the coding sequences of samples from over 8,000 cancer cases using Pindel-C. We discovered 285 complex indels in cancer-associated genes (such as PIK3R1, TP53, ARID1A, GATA3 and KMT2D) in approximately 3.5% of cases analyzed; nearly all instances of complex indels were overlooked (81.1%) or misannotated (17.6%) in previous reports of 2,199 samples. In-frame complex indels are enriched in PIK3R1 and EGFR, whereas frameshifts are prevalent in VHL, GATA3, TP53, ARID1A, PTEN and ATRX. Furthermore, complex indels display strong tissue specificity (such as VHL in kidney cancer samples and GATA3 in breast cancer samples). Finally, structural analyses support findings of previously missed, but potentially druggable, mutations in the EGFR, MET and KIT oncogenes. This study indicates the critical importance of improving complex indel discovery and interpretation in medical research.