Medicine and Health Sciences Commons^™

A Next Generation Sequencing-Based Protocol For Screening Of Variants Of Concern In Autism Spectrum Disorder, Jie Huang, Jun Liu, Ruiyi Tian, Kevin Liu, Patrick Zhuang, Hannah Tayla Sherman, Christoph Budjan, Michelle Fong, Min-Seo Jeong, Xue-Jun Kong

2020-Current year OA Pubs

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic influences. There is an increasing demand for ASD genetic testing beyond the traditionally recommended microarray and syndromic autism testing; however, the current whole genome sequencing (WGS) and whole exome sequencing (WES) methods are lacking an academic standard for WGS variant annotation, reporting, and interpretation, tailored towards patients with ASD and offer very limited interpretation for clinical significance. Using WGS data from six family trios, we demonstrate the clinical feasibility and technical implementation of an evidence-based, fully transparent bioinformatics pipeline and report framework for an ASD-focused WGS genetic report. We …

Risk Factors For Progression Or Death After First-Line Platinum-Based Chemotherapy In Real-World Patients In The Usa With Ovarian Cancer From 2011 To 2018, Shannon N Westin, Melinda Louie-Gao, Divya Gupta, Premal H Thaker

2020-Current year OA Pubs

No abstract provided.

Somatic Pik3r1 Variation As A Cause Of Vascular Malformations And Overgrowth, Catherine E Cottrell, Jonathan W Heusel, Meagan Corliss, Michael J Evenson, Carrie C Coughlin, Et Al.

2020-Current year OA Pubs

PURPOSE: Somatic activating variants in the PI3K-AKT pathway cause vascular malformations with and without overgrowth. We previously reported an individual with capillary and lymphatic malformation harboring a pathogenic somatic variant in PIK3R1, which encodes three PI3K complex regulatory subunits. Here, we investigate PIK3R1 in a large cohort with vascular anomalies and identify an additional 16 individuals with somatic mosaic variants in PIK3R1.

METHODS: Affected tissue from individuals with vascular lesions and overgrowth recruited from a multisite collaborative network was studied. Next-generation sequencing targeting coding regions of cell-signaling and cancer-associated genes was performed followed by assessment of variant pathogenicity.

RESULTS: The …

Coding And Noncoding Variants In Ebf3 Are Involved In Hadds And Simplex Autism, Evin M Padhi, Jeffrey K Ng, Elvisa Mehinovic, Tychele N Turner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Previous research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737. …

The Rare C9 P167s Risk Variant For Age-Related Macular Degeneration Increases Polymerization Of The Terminal Component Of The Complement Cascade, O Mcmahon, A Java, J P Atkinson, Et Al.

2020-Current year OA Pubs

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma …

Cancer-Associated Mutations Reveal A Novel Role For Epcam As An Inhibitor Of Cathepsin-L And Tumor Cell Invasion, Narendra V Sankpal, Taylor C Brown, Timothy P Fleming, John M Herndon, Anusha A Amaravati, Allison N Loynd, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: EpCAM (Epithelial cell adhesion molecule) is often dysregulated in epithelial cancers. Prior studies implicate EpCAM in the regulation of oncogenic signaling pathways and epithelial-to-mesenchymal transition. It was recently demonstrated that EpCAM contains a thyroglobulin type-1 (TY-1) domain. Multiple proteins with TY-1 domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor cell invasion and metastasis. Analysis of human cancer sequencing studies reveals that somatic EpCAM mutations are present in up to 5.1% of tested tumors.

METHODS: The Catalogue of Somatic Mutations in Cancer (COSMIC) database was queried to tabulate the position and amino acid changes of …

Pfmfr3: A Multidrug-Resistant Modulator In Plasmodium Falciparum, Frances Rocamora, Purva Gupta, Eva S Istvan, Madeline R Luth, Emma F Carpenter, Krittikorn Kümpornsin, Erika Sasaki, Jaeson Calla, Nimisha Mittal, Krypton Carolino, Edward Owen, Manuel Llinás, Sabine Ottilie, Daniel E Goldberg, Marcus C S Lee, Elizabeth A Winzeler

2020-Current year OA Pubs

In malaria, chemical genetics is a powerful method for assigning function to uncharacterized genes. MMV085203 and GNF-Pf-3600 are two structurally related napthoquinone phenotypic screening hits that kill both blood- and sexual-stage

Relationship Between Clinicopathologic Factors And Fdg Avidity In Radioiodine-Negative Recurrent Or Metastatic Differentiated Thyroid Carcinoma, Le Ngoc Ha, Amir Iravani, Nguyen Thi Nhung, Ngo Thi Minh Hanh, Febby Hutomo, Mai Hong Son

2020-Current year OA Pubs

BACKGROUND: In this study, we investigated the relationship between clinicopathologic factors, BRAF

METHODS: From 2015 to 2018 all patients with suspected recurrent or metastatic radioiodine-negative DTC patients who underwent FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. Suspected lesions on FDG PET/CT were biopsied and underwent BRAF

RESULTS: Sixty-three consecutive patients, 55 (87.3%) female, with median age of 48 (range 17-81) were included. The majority of patients had BRAF

CONCLUSION: The majority of recurrent or metastatic RAI-negative DTC have BRAF