The impact of chromosomal microarray on clinical management: a retrospective analysis

Henderson, Lindsay B.; Applegate, Carolyn D.; Wohler, Elizabeth; Sheridan, Molly B.; Hoover‐Fong, Julie; Batista, Denise

doi:10.1038/gim.2014.18

Cited by 69 publications

(67 citation statements)

References 28 publications

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“…Current single-gene disorder analyses or chromosomal microarray analyses have a diagnostic rate of ~13-14% in these patient populations, emphasizing the need for new molecular technologies. 26,27 Several previous reports using a trio-based WES strategy in large, specific patient populations reported diagnostic yields of ~25%, with some smaller studies reporting yields of up to 45-55%. 7,20,[28][29][30] The yield in this study is comparable to the 25% from these large patient population yields, and it demonstrates the power of WES to identify the genetic cause of disease in cohorts of intellectually disabled patients.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability

Monroe

Frederix

Savelberg

et al. 2016

Genetics in Medicine

152

140

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Purpose: This study investigated whole-exome sequencing (WES) yield in a subset of intellectually disabled patients referred to our clinical diagnostic center and calculated the total costs of these patients' diagnostic trajectory in order to evaluate early WES implementation. Methods:We compared 17 patients' trio-WES yield with the retrospective costs of diagnostic procedures by comprehensively examining patient records and collecting resource use information for each patient, beginning with patient admittance and concluding with WES initiation. We calculated cost savings using scenario analyses to evaluate the costs replaced by WES when used as a first diagnostic tool.Results: WES resulted in diagnostically useful outcomes in 29.4% of patients. The entire traditional diagnostic trajectory average cost was $16,409 per patient, substantially higher than the $3,972 trio-WES cost. WES resulted in average cost savings of $3,547 for genetic and metabolic investigations in diagnosed patients and $1,727 for genetic investigations in undiagnosed patients. Conclusion:The increased causal variant detection yield by WES and the relatively high costs of the entire traditional diagnostic trajectory suggest that early implementation of WES is a relevant and costefficient option in patient diagnostics. This information is crucial for centers considering implementation of WES and serves as input for future value-based research into diagnostics. Genet Med advance online publication 4 February 2016

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Section: Discussionmentioning

confidence: 99%

Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability

Monroe

Frederix

Savelberg

et al. 2016

Genetics in Medicine

152

140

View full text Add to dashboard Cite

show abstract

“…7,8 Two other studies reported on retrospective cohorts for which actual rates of clinical implications were available and found that more than 50% of all patients with abnormalities had clinical management changes based on microarray results. 9,11 Although microarrays are now common first-tier tests in this patient population and Original research article supported by medical guidelines from the American College of Medical Genetics and Genomics (ACMG), 12 the International Collaboration for Clinical Genomics (ISCA/ICCG), 5 and the American Academy of Neurology, 13 payer reimbursement for testing is inconsistent, indicating the need for additional systematic studies assessing the changes in patient management that occur as a result of microarray testing.…”

Section: Introductionmentioning

confidence: 99%

Clinical performance of the CytoScan Dx Assay in diagnosing developmental delay/intellectual disability

Pfundt

Kwiatkowski²,

Roter³

et al. 2016

Genetics in Medicine

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“…[3][4][5] In recent years, the implementation of highthroughput technologies, such as next-generation sequencing (NGS), array comparative genomic hybridization and single-nucleotide polymorphism (SNP) arrays, has facilitated and expedited the discovery of numerous genes that cause or contribute to various forms of ID. 6,7 Out of the autosomal genes known to have a role in severe ID, the dual-specificity tyrosine-phosphorylation-regulated kinase (DYRK1A) gene (OMIM 600855) has been one of the most extensively studied. [8][9][10][11] Interest in DYRK1A originated because of its genomic localization within the Down syndrome critical region (DSCR) on chromosome 21q22, a chromosomal region that is presumed to be largely responsible for the neuropathologic abnormalities observed in Down syndrome.…”

Section: Introductionmentioning

confidence: 99%

Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A

et al. 2015

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The dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene, located on chromosome 21q22.13 within the Down syndrome critical region, has been implicated in syndromic intellectual disability associated with Down syndrome and autism. DYRK1A has a critical role in brain growth and development primarily by regulating cell proliferation, neurogenesis, neuronal plasticity and survival. Several patients have been reported with chromosome 21 aberrations such as partial monosomy, involving multiple genes including DYRK1A. In addition, seven other individuals have been described with chromosomal rearrangements, intragenic deletions or truncating mutations that disrupt specifically DYRK1A. Most of these patients have microcephaly and all have significant intellectual disability. In the present study, we report 10 unrelated individuals with DYRK1A-associated intellectual disability (ID) who display a recurrent pattern of clinical manifestations including primary or acquired microcephaly, ID ranging from mild to severe, speech delay or absence, seizures, autism, motor delay, deep-set eyes, poor feeding and poor weight gain. We identified unique truncating and non-synonymous mutations (three nonsense, four frameshift and two missense) in DYRK1A in nine patients and a large chromosomal deletion that encompassed DYRK1A in one patient. On the basis of increasing identification of mutations in DYRK1A, we suggest that this gene be considered potentially causative in patients presenting with ID, primary or acquired microcephaly, feeding problems and absent or delayed speech with or without seizures.

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The impact of chromosomal microarray on clinical management: a retrospective analysis

Cited by 69 publications

References 28 publications

Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability

Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability

Clinical performance of the CytoScan Dx Assay in diagnosing developmental delay/intellectual disability

Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A

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