Comprehensive Analysis of TEK Variants in Patients With Vascular Malformations.

Pathogenic variants in the receptor tyrosine kinase TIE2, encoded by TEK, are known to cause vascular malformations (VMs). In this study, we retrospectively reviewed the deidentified data generated through clinical NGS testing in our laboratory and found 88 VM cases with a total of 107 clinically significant TEK variants. Among those, 23 unique variants at the amino acid level were identified, including five novel (p.

Clinical whole-genome sequencing and FISH identify two different fusion partners for NUP98 in a patient with acute myeloid leukemia: A case report.

Background: Only rare cases of acute myeloid leukemia (AML) have been shown to harbor a t(8;11)(p11.2;p15.4).

High Coverage Highly Accurate Long-Read Sequencing of a Mouse Neuronal Cell Line Using the PacBio Revio Sequencer.

Recently, Pacific Biosciences released a new highly accurate long-read sequencer called the Revio System that is projected to generate 30× HiFi whole-genome sequencing for the human genome within one sequencing SMRT Cell. Mouse and human genomes are similar in size. In this study, we sought to test this new sequencer by characterizing the genome and epigenome of the mouse neuronal cell line Neuro-2a.

Profiling variants in disorders of somatic mosaicism.

Purpose: Variants in (encoding p110α; the catalytic subunit of PI3K) characterize some disorders of somatic mosaicism (DoSM) conditions with clinical features, including sporadic overgrowth and vascular malformations. Here, we profile variants in DoSM.

Methods: We applied a next-generation, sequencing-based, laboratory-developed test, using an average coverage of approximately 2000× for up to 37 genes associated with DoSM, on a cohort of 1197 patients with DoSM referred for clinical genomics services between 2013 and 2022.

Co-existence of 2 clinically significant variants causing disorders of somatic mosaicism.

Purpose: Disorders of somatic mosaicism (DoSM) are a heterogeneous group of conditions caused by postzygotic variants in genes within the PI3K/AKT/mTOR and RAS/MAPK signaling pathway. The co-existence of 2 activating variants in this disease group is extremely rare.

Methods: A deep sequencing next-generation sequencing assay for the molecular diagnosis of DoSM was run on 936 individuals with DoSM.

Comparing Gene Panels for Non-Retinal Indications: A Systematic Review.

Importance: The options for genetic testing continue to grow for ocular conditions, including optic atrophy, anterior segment dysgenesis, cataracts, corneal dystrophy, nystagmus, and glaucoma. Gene panels can vary in content and coverage, as we and others have evaluated in inherited retinal disease (IRD).

Objective: To describe gene panel testing options for inherited eye disease phenotypes and their differences.

High-depth next-generation sequencing panel testing in the evaluation of arteriovenous malformations.

Arteriovenous malformations (AVMs) are vascular lesions in which an overgrowth of blood vessels of varying sizes develops with one or more direct connections between the arterial and venous circulation. We performed a retrospective review of a cohort of 54 patients with AVMs referred to our clinical genomic laboratory for high-depth next-generation sequencing (NGS) panel of Disorders of Somatic Mosaicism (DoSM). Thirty-seven of 54 patients were female (68.

A comparative analysis of RAS variants in patients with disorders of somatic mosaicism.

Purpose: RAS genes (HRAS, KRAS, and NRAS) are commonly found to be mutated in cancers, and activating RAS variants are also found in disorders of somatic mosaicism (DoSM). A survey of the mutational spectrum of RAS variants in DoSM has not been performed.

Methods: A total of 938 individuals with suspected DoSM underwent high-sensitivity clinical next-generation sequencing-based testing.

Modifications to student quarantine policies in K-12 schools implementing multiple COVID-19 prevention strategies restores in-person education without increasing SARS-CoV-2 transmission risk, January-March 2021.

Objective: To determine whether modified K-12 student quarantine policies that allow some students to continue in-person education during their quarantine period increase schoolwide SARS-CoV-2 transmission risk following the increase in cases in winter 2020-2021.

Methods: We conducted a prospective cohort study of COVID-19 cases and close contacts among students and staff (n = 65,621) in 103 Missouri public schools. Participants were offered free, saliva-based RT-PCR testing.

Outpatient Primary Care Genetic Testing Primer: What to Order and Testing Considerations.

The field of genetics has evolved rapidly over the last few decades, from testing methods to genetic diagnoses, bringing new genetic testing guidelines and considerations for health care providers. Overall geneticists are limited in number and availability, particularly in non-academic settings, and many patients first present to a primary care provider. Here, we aim to review various modalities of genetic testing, their indications, limitations, and other pretest considerations for the primary care provider.

Assessing COVID-19 testing strategies in K-12 schools in underserved populations: study protocol for a cluster-randomized trial.

Background: Since March 2020, COVID-19 has disproportionately impacted communities of color within the United States. As schools have shifted from virtual to in-person learning, continual guidance is necessary to understand appropriate interventions to prevent SARS-CoV-2 transmission. Weekly testing of students and staff for SARS-CoV-2 within K-12 school setting could provide an additional barrier to school-based transmission, especially within schools unable to implement additional mitigation strategies and/or are in areas of high transmission.

Clinical whole-genome sequencing in cancer diagnosis.

Characterizing the genomic landscape of cancers is a routine part of clinical care that began with the discovery of the Philadelphia chromosome and has since coevolved with genomic technologies. Genomic analysis of tumors at the nucleotide level using DNA sequencing has revolutionized the understanding of cancer biology and identified new molecular drivers of disease that have led to therapeutic advances and improved patient outcomes. However, the application of next-generation sequencing in the clinical laboratory has generally been limited until very recently to targeted analysis of selected genes.

From karyotypes to precision genomics in 9p deletion and duplication syndromes.

While 9p deletion and duplication syndromes have been studied for several years, small sample sizes and minimal high-resolution data have limited a comprehensive delineation of genotypic and phenotypic characteristics. In this study, we examined genetic data from 719 individuals in the worldwide 9p Network Cohort: a cohort seven to nine times larger than any previous study of 9p. Most breakpoints occur in bands 9p22 and 9p24, accounting for 35% and 38% of all breakpoints, respectively.

SARS-CoV-2 screening testing in schools for children with intellectual and developmental disabilities.

Background: Transmission of SARS-CoV-2 in schools primarily for typically developing children is rare. However, less is known about transmission in schools for children with intellectual and developmental disabilities (IDD), who are often unable to mask or maintain social distancing. The objectives of this study were to determine SARS-CoV-2 positivity and in-school transmission rates using weekly screening tests for school staff and students and describe the concurrent deployment of mitigation strategies in six schools for children with IDD.

SARS-CoV-2 Screening Testing in Schools for Children with Intellectual and Developmental Disabilities.

BACKGROUNDTransmission of SARS-CoV-2 in schools primarily for typically developing children is rare. However, less is known about transmission in schools for children with intellectual and developmental disabilities (IDD), who are often unable to mask or maintain social distancing. The objectives of this study were to determine SARS-CoV-2 positivity and in-school transmission rates using weekly screening tests for school staff and students and describe the concurrent deployment of mitigation strategies in six schools for children with IDD.

Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers.

Background: Genomic analysis is essential for risk stratification in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). Whole-genome sequencing is a potential replacement for conventional cytogenetic and sequencing approaches, but its accuracy, feasibility, and clinical utility have not been demonstrated.

Methods: We used a streamlined whole-genome sequencing approach to obtain genomic profiles for 263 patients with myeloid cancers, including 235 patients who had undergone successful cytogenetic analysis.

Tumor mutation burden and checkpoint immunotherapy markers in primary and metastatic synovial sarcoma.

Synovial sarcoma (SS) is a soft-tissue malignancy that most often affects patients aged between 15 and 40 years, and the prognosis for patients with metastatic disease is generally poor. This study was performed to evaluate checkpoint blockade immunotherapy markers in SS, including tumor mutational burden (TMB), DNA mismatch repair (MMR) status, and PDL-1 (programmed cell death ligand 1), PD1 (programmed cell death 1), and CD8 expression by normal-tumor paired whole-exome sequencing (WES) and immunohistochemistry (IHC). Outcomes evaluated included event-free and overall survival.