Assessing the utility of confirmatory studies following identification of large-scale genomic imbalances by microarray

Sanmann, Jennifer N.; Pickering, Diane L.; Golden, Denae M.; Stevens, Jadd M.; Hempel, T.; Althof, Pamela A.; Wiggins, Michele L.; Starr, Lois J.; Davé, Bhavana J.; Sanger, Warren G.

doi:10.1038/gim.2014.204

Cited by 6 publications

(8 citation statements)

References 10 publications

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“…These cases include ring and marker chromosomes as well as other complex rearrangements. 8, 28, 29 This additional testing to clarify the genetic mechanism associated with the CNVs is necessary for accurate recurrence risk counseling.…”

Section: Resultsmentioning

confidence: 99%

Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Waggoner

Wain

Dubuc

et al. 2018

Genetics in Medicine

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Section: Resultsmentioning

confidence: 99%

Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Waggoner

Wain

Dubuc

et al. 2018

Genetics in Medicine

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“…In 2010, CMA was recommended as a first-tier diagnostic tool for patients with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA) [23]. CMA results have shown perfect concordance with results from FISH or multiplex ligation-dependent probe amplification (MLPA), and provide a much higher diagnostic yield than traditional karyotyping (15–20% vs 3%) [24].…”

Section: Introductionmentioning

confidence: 99%

Chromosomal Microarray Analysis as a First-Tier Clinical Diagnostic Test in Patients With Developmental Delay/Intellectual Disability, Autism Spectrum Disorders, and Multiple Congenital Anomalies: A Prospective Multicenter Study in Korea

et al. 2019

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Background To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA). Methods We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results. Results A total of 122 patients (19.8%) had abnormal CMA results, with either pathogenic variants (N=65) or variants of possible significance (VPS, N=57). Thirty-five well-known diseases were detected: 16p11.2 microdeletion syndrome was the most common, followed by Prader-Willi syndrome, 15q11-q13 duplication, Down syndrome, and Duchenne muscular dystrophy. Variants of unknown significance (VUS) were discovered in 51 patients (8.3%). VUS of genes putatively associated with developmental disorders were found in five patients: IMMP2L deletion, PTCH1 duplication, and ATRNL1 deletion. CMA results influenced clinical management, such as imaging studies, specialist referral, and laboratory testing in 71.4% of patients overall, and in 86.0%, 83.3%, 75.0%, and 67.3% of patients with VPS, pathogenic variants, VUS, and benign variants, respectively. Conclusions Clinical application of CMA as a first-tier test improves diagnostic yields and the quality of clinical management in patients with DD/ID, ASD, and MCA.

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“…Previous WES studies revealed a diagnosis rate of ∼25-30% in nonselective patients (Yang et al, 2013(Yang et al, , 2014Lee et al, 2014;Daoud et al, 2016;Retterer et al, 2016). Moreover, additional pathogenic and likely pathogenic CNVs were also identified in over 10% of patients (Sanmann et al, 2015;Homma et al, 2018;Jang et al, 2019). The development of NGS data based CNV calling algorithm makes it possible to identify SNVs and CNVs at same time.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, multiple researches on clinical utility and cost of WES have provided evidence endorsing it as a first-tier test for children with suspected monogenic disorders (Nguyen and Charlebois, 2015;Monroe et al, 2016;Stark et al, 2016;Hu et al, 2018). CMA has been used as a first-tier clinical diagnostic test in patients with developmental delay (DD)/intellectual disability (ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA) since 2010 (Manning et al, 2010;Miller et al, 2010); and copy number variants (CNVs) detected by CMA explained the pathogenesis for over 10% of these cases (Sanmann et al, 2015;Homma et al, 2018;Jang et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Parallel Tests of Whole Exome Sequencing and Copy Number Variant Sequencing Increase the Diagnosis Yields of Rare Pediatric Disorders

Guo

et al. 2020

Front. Genet.

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Background: Both whole exome sequencing and copy number variants sequencing were applied to identify the genetic cause of rare pediatric disorders. In our study, we aimed to investigate the diagnostic yield of parallel tests of trio whole exome sequencing and copy number variants sequencing and its clinical utility. Methods: After collecting detailed clinical information, a total of 60 patients were referred to parallel tests of whole exome sequencing and copy number variants sequencing, which used shared initial libraries. Results: 26 pathogenic or likely pathogenic single nucleotide variants and 11 copy number variants were identified in 32 patients. 65.4% (17/26) of the SNVs were novel. The overall diagnosis rate was 53.3%. For the patients with positive results, 22 (36.7%) patients were diagnosed by whole exome sequencing and 10 (16.7%) patients were diagnosed by copy number variants sequencing. We also reviewed clinical impact on selected cases. Conclusion: We adopted an approach by performing parallel tests of trio whole exome sequencing and copy number variants sequencing with shared initial libraries. This strategy is relatively efficient and cost-effective for the diagnosis of rare pediatric disorders with high heterogeneity.

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Assessing the utility of confirmatory studies following identification of large-scale genomic imbalances by microarray

Cited by 6 publications

References 10 publications

Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Chromosomal Microarray Analysis as a First-Tier Clinical Diagnostic Test in Patients With Developmental Delay/Intellectual Disability, Autism Spectrum Disorders, and Multiple Congenital Anomalies: A Prospective Multicenter Study in Korea

Parallel Tests of Whole Exome Sequencing and Copy Number Variant Sequencing Increase the Diagnosis Yields of Rare Pediatric Disorders

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