scholarly journals Increased Diagnostic Yield of Array Comparative Genomic Hybridization for Autism Spectrum Disorder in One Institution in Taiwan

Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 15
Author(s):  
Chung-Lin Lee ◽  
Chih-Kuang Chuang ◽  
Ru-Yi Tu ◽  
Huei-Ching Chiu ◽  
Yun-Ting Lo ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Comparative Genomic Hybridization ◽  
Array Comparative Genomic Hybridization ◽  
Array Cgh ◽  
Diagnostic Yield ◽  
Autism Spectrum ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Clinically Significant ◽  
Genomic Variant

Background and Objectives: Chromosomal microarray offers superior sensitivity for identification of submicroscopic copy number variants (CNVs) and is recommended for the initial genetic testing of patients with autism spectrum disorder (ASD). This study aims to determine the diagnostic yield of array comparative genomic hybridization (array-CGH) in ASD patients from a cohort of Chinese patients in Taiwan. Materials and Methods: Enrolled in this study were 80 ASD children (49 males and 31 females; 2–16 years old) followed up at Taipei MacKay Memorial Hospital between January 2010 and December 2020. The genomic DNA extracted from blood samples was analyzed by array-CGH via the Affymetrix GeneChip Genome-Wide Human single nucleotide polymorphism (SNP) and NimbleGen International Standards for Cytogenomic Arrays (ISCA) Plus Cytogenetic Arrays. The CNVs were classified into five groups: pathogenic (pathologic variant), likely pathogenic (potential pathologic variant), likely benign (potential normal genomic variant), benign (normal genomic variant), and uncertain clinical significance (variance of uncertain significance), according to the American College of Medical Genetics (ACMG) guidelines. Results: We identified 47 CNVs, 31 of which in 27 patients were clinically significant. The overall diagnostic yield was 33.8%. The most frequently clinically significant CNV was 15q11.2 deletion, which was present in 4 (5.0%) patients. Conclusion: In this study, a satisfactory diagnostic yield of array-CGH was demonstrated in a Taiwanese ASD patient cohort, supporting the clinical usefulness of array-CGH as the first-line testing of ASD in Taiwan.

Clinical Utility of Array Comparative Genomic Hybridization for Detection of Chromosomal Abnormalities in Pediatric Acute Lymphoblastic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2275-2275
Author(s):  
Karen Rabin ◽  
Chris Man ◽  
Sharon Plon ◽  
Pulivarthi Rao ◽  
Rizwan Naeem
Keyword(s):  
Comparative Genomic Hybridization ◽  
Clinical Utility ◽  
Array Comparative Genomic Hybridization ◽  
Array Cgh ◽  
Lymphoblastic Leukemia ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Structural Abnormalities ◽  
Pediatric All ◽  
Balanced Translocations

Abstract Chromosomal structural abnormalities in ALL are powerful independent predictors of prognosis, and directly impact choice of therapy. Currently, clinical detection of these abnormalities is based on karyotype and fluorescent in-situ hybridization (FISH), but these methods have limitations. Under optimal circumstances, structural abnormalities are detectable in well over 90% of ALL cases, but in actuality, typical cytogenetic laboratories demonstrate only a 50–60% abnormality detection rate. Karyotype may fail due to unsuccessful cell growth in culture and/or relative overgrowth of normal lymphocytes. FISH is limited by the expense and labor intensity of performing a separate assay for each probe used. Array comparative genomic hybridization (CGH) may have clinical utility as a complementary diagnostic tool in pediatric ALL. Its advantages include the ability to detect copy number changes in regions too small to be identifiable by karyotype; to identify novel abnormalities for which specific FISH probes do not exist in current diagnostic laboratories; and to provide information in as many as 50% of cases which show a failed or normal karyotype. In addition to its clinical utility, array CGH provides a wealth of information which may be mined for discovery of new pathways in leukemogenesis and additional prognostic factors within existing disease subgroups. The main limitation of array CGH is its inability to detected balanced translocations. We evaluated the diagnostic utility of a bacterial artificial chromosome (BAC) array CGH platform, the SpectralChip 2600, with an average resolution of 1.0 MB across the genome. We analyzed 50 pediatric ALL bone marrow specimens obtained at diagnosis, and compared the findings to the clinical results based on karyotype and standard 5-probe FISH panel. The cases ranged from 1–15 years (mean 5 years), with marrow containing between 33–94% leukemic blasts (mean 77%). Each sample was hybridized to the chip with a healthy control of the opposite gender. The sensitivity of array CGH in detecting abnormalities identified by karyotype and FISH was approximately 88%. Several of the abnormalities “missed” by CGH, which lowered the sensitivity score, were subsequently found to be erroneous karyotype calls when followed up with specific FISH probes. In addition, array CGH detected numerous additional areas of amplification and deletion which were subsequently validated by FISH, including in 10 cases for which cytogenetics was either normal or unsuccessful. Loss of 1p31, loss of 7p21, and gain of 16p13 were aberrations that were each noted to occur in three or more different cases, and hence may be worthy of further study. In the future, development of a customized ALL chip which is enriched for probes at sites of known amplification and deletion could further heighten diagnostic sensitivity, obviate the need for performance of multiple FISH tests, and provide valuable information in the substantial number of cases with a normal or failed karyotype analysis. Balanced translocations would still require testing via a multiplex PCR assay or a combination of available FISH probes.

scholarly journals Development of a Focused Oligonucleotide-Array Comparative Genomic Hybridization Chip for Clinical Diagnosis of Genomic Imbalance

2007 ◽  
Vol 53 (12) ◽  
pp. 2051-2059 ◽  
Author(s):  
Yiping Shen ◽  
David T Miller ◽  
Sau Wai Cheung ◽  
Va Lip ◽  
Xiaoming Sheng ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Comparative Genomic Hybridization ◽  
Array Comparative Genomic Hybridization ◽  
Developmental Disorders ◽  
Array Cgh ◽  
Clinical Laboratory ◽  
Oligonucleotide Array ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Genomic Imbalance

Abstract Background: Submicroscopic genomic imbalance underlies well-defined microdeletion and microduplication syndromes and contributes to general developmental disorders such as mental retardation and autism. Array comparative genomic hybridization (CGH) complements routine cytogenetic methods such as karyotyping and fluorescence in situ hybridization (FISH) for the detection of genomic imbalance. Oligonucleotide arrays in particular offer advantages in ease of manufacturing, but standard arrays for single-nucleotide polymorphism genotyping or linkage analysis offer variable coverage in clinically relevant regions. We report the design and validation of a focused oligonucleotide-array CGH assay for clinical laboratory diagnosis of genomic imbalance. Methods: We selected >10 000 60-mer oligonucleotide features from Agilent’s eArray probe library to interrogate all subtelomeric and pericentromeric regions and 95 additional clinically relevant regions for a total of 179 loci. Sensitivity and specificity were measured for 105 patient samples, including 51 with known genomic-imbalance events, as detected by bacterial artificial chromosome–based array CGH, FISH, or multiplex ligation-dependent probe amplification. Results: Focused array CGH detected all known regions of genomic imbalance in 51 validation samples with 100% concordance and an excellent signal-to-noise ratio. The mean SD among log2 ratios of all noncontrol features without copy number alteration was 0.062 (median, 0.055). Clinical testing of another 211 samples from individuals with developmental delay, unexplained mental retardation, dysmorphic features, or multiple congenital anomalies revealed genomic imbalance in 25 samples (11.9%). Conclusions: This focused oligonucleotide-array CGH assay, a flexible, robust method for clinically diagnosing genetic disorders associated with genomic imbalance, offers appreciable advantages over currently available platforms.

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