Dataset Information

When moments matter: Finding answers with rapid exome sequencing.

ABSTRACT: BACKGROUND:When time is of the essence in critical care cases, a fast molecular diagnosis is often necessary to help health care providers quickly determine best next steps for treatments, prognosis, and counseling of their patients. In this paper, we present the diagnostic rates and improved quality of life for patients undergoing clinical rapid exome sequencing. METHODS:The clinical histories and results of 41 patients undergoing rapid exome sequencing were retrospectively reviewed. RESULTS:Clinical rapid exome sequencing identified a definitive diagnosis in 13/41 (31.7%) and other relevant findings in 17 of the patients (41.5%). The average time to verbal report was 7 days; to written report was 11 days. CONCLUSIONS:Our observations demonstrate the utility and effectiveness of rapid family-based diagnostic exome sequencing in improving patients care.

SUBMITTER: Powis Z

PROVIDER: S-EPMC7005623 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

When moments matter: Finding answers with rapid exome sequencing.

Powis Zöe Z Farwell Hagman Kelly D KD Blanco Kirsten K Au Margaret M Graham John M JM Singh Kathryn K Gallant Natalie N Randolph Linda M LM Towne Meghan M Hunter Jesse J Shinde Deepali N DN Palmaer Erika E Schoenfeld Brian B Tang Sha S

Molecular genetics & genomic medicine 20191224 2

<h4>Background</h4>When time is of the essence in critical care cases, a fast molecular diagnosis is often necessary to help health care providers quickly determine best next steps for treatments, prognosis, and counseling of their patients. In this paper, we present the diagnostic rates and improved quality of life for patients undergoing clinical rapid exome sequencing.<h4>Methods</h4>The clinical histories and results of 41 patients undergoing rapid exome sequencing were retrospectively revie ...[more]

PMID: 31872981

Similar Datasets

Project description:BackgroundPrenatal exome sequencing (ES) for the diagnosis of fetal anomalies was implemented nationally in England in October 2020 by the NHS Genomic Medicine Service (GMS). is the GMS is based around seven regional Genomic Laboratory Hubs (GLHs). Prenatal ES has the potential to significantly improve NHS prenatal diagnostic services by increasing genetic diagnoses and informing prenatal decision-making. Prenatal ES has not previously been offered routinely in a national healthcare system and there are gaps in knowledge and guidance.MethodsOur mixed-methods evaluation commenced in October 2020, aligning with the start date of the NHS prenatal ES service . Study design draws on a framework developed in previous studies of major system innovation. There are five interrelated workstreams. Workstream-1 will use interviews and surveys with professionals, non-participant observations and documentary analysis to produce in-depth case studies across all GLHs. Data collection at multiple time points will track changes over time. In Workstream-2 qualitative interviews with parents offered prenatal ES will explore experiences and establish information and support needs. Workstream-3 will analyse data from all prenatal ES tests for nine-months to establish service outcomes (e.g. diagnostic yield, referral rates, referral sources). Comparisons between GLHs will identify factors (individual or service-related) associated with any variation in outcomes. Workstream-4 will identify and analyse practical ethical problems. Requirements for an effective ethics framework for an optimal and equitable service will be determined. Workstream-5 will assess costs and cost-effectiveness of prenatal ES versus standard tests and evaluate costs of implementing an optimal prenatal ES care pathway. Integration of findings will determine key features of an optimal care pathway from a service delivery, parent and professional perspective.DiscussionThe proposed formative and summative evaluation will inform the evolving prenatal ES service to ensure equity of access, high standards of care and benefits for parents across England.

Project description:BACKGROUND:Tandem mass spectrometry (MS MS) and simple fluorometric assays are currently used in newborn screening programs to detect inborn errors of metabolism (IEM). The aim of the study was to evaluate the clinical utility of exome sequencing as a second tier screening method to assist clinical diagnosis of the newborn. METHODS:A novel PCR-exome amplification and re-sequencing (PEARS) assay was designed and used to detect mutations in 122 genes associated with 101 IEM. Newborn bloodspots positive by biochemical testing were analysed by PEARS assay to detect pathogenic mutations relevant to the IEM. RESULTS:In initial validation studies of genomic DNA samples, PEARS assay correctly detected 25 known mutations associated with 17 different IEM. Retrospective gene analysis of newborns with clinical phenylketonuria (PKU), identified compound heterozygote phenylalanine hydroxylase (PAH) gene mutations in eight of nine samples (89%). Prospective analysis of 211 bloodspots correctly identified the two true PKU samples, yielding positive and negative predictive values of 100%. Testing of 8 true positive MS MS samples correctly identified potentially pathogenic compound heterozygote genotypes in 2 cases of citrullinemia type 1 and one case each of methylmalonic acidemia, isobutyryl-CoA dehydrogenase deficiency, short chain acyl-CoA dehydrogenase deficiency and glutaric acid type II and heterozygous genotypes in 2 cases of autosomal dominant methioninemia. Analysis of 11 of 12 false positive MS MS samples for other IEM identified heterozygous carriers in 8 cases for the relevant genes associated with the suspected IEM. In the remaining 3 cases, the test revealed compound heterozygote mutations in other metabolic genes not associated with the suspected IEM, indicating a misinterpretation of the original MS MS data. CONCLUSIONS:The PEARS assay has clinical utility as a rapid and cost effective second-tier test to assist the clinician to accurately diagnose newborns with a suspected IEM.

Project description:Balance recovery after tripping often requires an active adaptation of foot placement. Thus far, few attempts have been made to actively assist forward foot placement for balance recovery employing wearable devices. This study aims to explore the possibilities of active forward foot placement through two paradigms of actuation: assistive moments exerted with the reaction moments either internal or external to the human body, namely 'joint' moments and 'free' moments, respectively. Both paradigms can be applied to manipulate the motion of segments of the body (e.g., the shank or thigh), but joint actuators also exert opposing reaction moments on neighbouring body segments, altering posture and potentially inhibiting tripping recovery. We therefore hypothesised that a free moment paradigm is more effective in assisting balance recovery following tripping. The simulation software SCONE was used to simulate gait and tripping over various ground-fixed obstacles during the early swing phase. To aid forward foot placement, joint moments and free moments were applied either on the thigh to augment hip flexion or on the shank to augment knee extension. Two realizations of joint moments on the hip were simulated, with the reaction moment applied to either the pelvis or the contralateral thigh. The simulation results show that assisting hip flexion with either actuation paradigm on the thigh can result in full recovery of gait with a margin of stability and leg kinematics closely matching the unperturbed case. However, when assisting knee extension with moments on the shank, free moment effectively assist balance but joint moments with the reaction moment on the thigh do not. For joint moments assisting hip flexion, placement of the reaction moment on the contralateral thigh was more effective in achieving the desired limb dynamics than placing the reaction on the pelvis. Poor choice of placement of reaction moments may therefore have detrimental consequences for balance recovery, and removing them entirely (i.e., free moment) could be a more effective and reliable alternative. These results challenge conventional assumptions and may inform the design and development of a new generation of minimalistic wearable devices to promote balance during gait.

Dataset Information

When moments matter: Finding answers with rapid exome sequencing.

Publications

When moments matter: Finding answers with rapid exome sequencing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets