Whole Exome Sequencing in Pediatric Neurology Patients

Nolan, Danielle; Carlson, Martha

doi:10.1177/0883073815627880

Cited by 63 publications

(15 citation statements)

References 10 publications

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“…Successful application of WES in pediatric neurology has been confined mostly to single case reports and retrospective studies in which WES was used as a last-resource genetic test. 5 , 6 , 7 , 8 , 9 , 10 , 11 However, prospective clinical utility studies of larger groups of patients have not yet been performed. Here, we present such data for a cohort of 150 patients who received both the standard diagnostic assessment and WES, allowing a direct comparison of the performance of both trajectories.…”

Section: Introductionmentioning

confidence: 99%

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

Vissers¹,

Nimwegen²,

Schieving

et al. 2017

Genetics in Medicine

226

212

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Purpose:Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation.Methods:We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene–based testing) and WES simultaneously.Results:Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted.Conclusion:Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.Genet Med advance online publication 23 March 2017

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Section: Introductionmentioning

confidence: 99%

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

Vissers¹,

Nimwegen²,

Schieving

et al. 2017

Genetics in Medicine

226

212

View full text Add to dashboard Cite

show abstract

“…In recent years, the cost of comprehensive genetic testing such as whole exome and genome sequencing (WES/WGS) has decreased enough to make it a cost-effective tool in the diagnosis of individuals with suspected genetic conditions (Nolan & Carlson, 2016;Stark et al, 2017). Through use of this technology, patients and families who have been searching for answers for years are finally given an explanation (Lee et al, 2014;de Ligt et al, 2012;Sawyer et al, 2016;Shashi et al, 2014;Yang et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Cases from the Undiagnosed Diseases Network: The continued value of counseling skills in a new genomic era

Macnamara

Schoch

Kelley

et al. 2019

Journal of Genetic Counseling

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The “diagnostic odyssey” is well known and described in genetic counseling literature. Studies addressing the psychological, emotional, and financial costs of not having a diagnosis have shown how it permeates the lives of patients and families. The Undiagnosed Diseases Network aims to end this odyssey by providing diagnoses to individuals with undiagnosed conditions through multidisciplinary evaluations, whole exome and genome sequencing, and basic science research. It also provides an opportunity to learn from patients and families and to better understand their journeys and the impact of receiving a diagnosis. Seven cases are presented that outline challenges that come from working with chronically undiagnosed and newly diagnosed patients in a time when sequencing for clinical diagnosis is rapidly increasing. They illuminate the emotional journey of patients and families searching for a diagnosis and the mental health problems, financial distress, and chaos that can accompany not having answers. They also illustrate the surprising reactions patients and families can have to receiving a diagnosis, including anger, grief, and disappointment. While the lessons learned from these families are not novel, new strategies are presented for handling these challenges in undiagnosed and ultra‐rare populations, groups that will increase with the rise of clinical sequencing.

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“…A recent paper estimated that with the use of WES there is the potential for an estimated average savings of $2465.62 and $502.52 (the average charge estimate on secondary genetic and metabolic testing, respectively) and up to $13,305.00 and $2340.00 (the maximum charge estimate on secondary genetic and metabolic testing, respectively). It is suggested that WES charge could be lower than the composite required for more conventional secondary genetic and metabolic laboratory testing [ 12 ]. Limiting the molecular screening to the Mendeliome, which comprehends the genes that are known to cause a Mendelian disorder, WES appears a highly informative and convenient first-tier tool in the diagnostic setting.…”

Section: Discussionmentioning

confidence: 99%

A mild form of adenylosuccinate lyase deficiency in absence of typical brain MRI features diagnosed by whole exome sequencing

et al. 2017

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BackgroundAdenylosuccinate lyase (ADSL) deficiency is a defect of purine metabolism affecting purinosome assembly and reducing metabolite fluxes through purine de novo synthesis and purine nucleotide recycling pathways. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The most severe form is characterized by neonatal encephalopathy, absence of spontaneous movement, respiratory failure, intractable seizures, and early death within the first weeks of life. More commonly, ADSL presents purely neurologic clinical picture characterized by severe psychomotor retardation, microcephaly, early onset of seizures, and autistic features (type I) or a more slowly progressing form with later onset, and major features including slight to moderate psychomotor retardation, and transient contact disturbances (type II). Diagnostic markers are the presence of succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (SAdo) in extracellular fluids. ADSL is a rare disorder, although its prevalence remains unknown. Of note, the wide range of essentially nonspecific manifestations and lack of awareness of the condition often prevent diagnosis.Case presentationWe present here the case of particularly mild, late onset ADSL that has been unsuccessfully investigated until whole exome sequencing (WES) was performed.ConclusionsBesides emphasizing the valuable diagnostic value of WES, this report provides new data further documenting the relatively wide clinical manifestation of ADSL.Electronic supplementary materialThe online version of this article (doi:10.1186/s13052-017-0383-7) contains supplementary material, which is available to authorized users.

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Whole Exome Sequencing in Pediatric Neurology Patients

Cited by 63 publications

References 10 publications

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

Cases from the Undiagnosed Diseases Network: The continued value of counseling skills in a new genomic era

A mild form of adenylosuccinate lyase deficiency in absence of typical brain MRI features diagnosed by whole exome sequencing

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