The clinical benefit of array-based comparative genomic hybridization for detection of copy number variants in Czech children with intellectual disability and developmental delay

Autor: Marketa Wayhelova, Petr Kuglík, Renata Gaillyová, Jan Smetana, Eva Hladílková, Vladimíra Vallová, Marta Hanáková, Marcela Vilémová, Petra Nikolova, Barbora Gromesova, Hana Filková
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
lcsh:Internal medicine
lcsh:QH426-470
Array-CGH
Adolescent
DNA Copy Number Variations
Developmental delay
Developmental Disabilities
CNV
Intellectual disability
Chromosomal translocation
Microduplication
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Genetics
medicine
Humans
Multiplex
Copy-number variation
Multiplex ligation-dependent probe amplification
lcsh:RC31-1245
Child
Genetics (clinical)
Czech Republic
Oligonucleotide Array Sequence Analysis
Comparative Genomic Hybridization
medicine.diagnostic_test
business.industry
Infant
Newborn
Infant
Human genetics
3. Good health
lcsh:Genetics
030104 developmental biology
Real-time polymerase chain reaction
030220 oncology & carcinogenesis
Child
Preschool
Microdeletion
Female
business
Fluorescence in situ hybridization
Comparative genomic hybridization
Research Article
Zdroj: BMC Medical Genomics
BMC Medical Genomics, Vol 12, Iss 1, Pp 1-11 (2019)
ISSN: 1755-8794
Popis: Background Chromosomal microarray analysis has been shown to be a valuable and cost effective assay for elucidating copy number variants (CNVs) in children with intellectual disability and developmental delay (ID/DD). Methods In our study, we performed array-based comparative genomic hybridization (array-CGH) analysis using oligonucleotide-based platforms in 542 Czech patients with ID/DD, autism spectrum disorders and multiple congenital abnormalities. Prior to the array-CGH analysis, all the patients were first examined karyotypically using G-banding. The presence of CNVs and their putative derivation was confirmed using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and predominantly relative quantitative polymerase chain reaction (qPCR). Results In total, 5.9% (32/542) patients were positive for karyotypic abnormalities. Pathogenic/likely pathogenic CNVs were identified in 17.7% of them (96/542), variants of uncertain significance (VOUS) were detected in 4.8% (26/542) and likely benign CNVs in 9.2% of cases (50/542). We identified 6.6% (36/542) patients with known recurrent microdeletion (24 cases) and microduplication (12 cases) syndromes, as well as 4.8% (26/542) patients with non-recurrent rare microdeletions (21 cases) and microduplications (5 cases). In the group of patients with submicroscopic pathogenic/likely pathogenic CNVs (13.3%; 68/510) we identified 91.2% (62/68) patients with one CNV, 5.9% (4/68) patients with two likely independent CNVs and 2.9% (2/68) patients with two CNVs resulting from cryptic unbalanced translocations. Of all detected CNVs, 21% (31/147) had a de novo origin, 51% (75/147) were inherited and 28% (41/147) of unknown origin. In our cohort pathogenic/likely pathogenic microdeletions were more frequent than microduplications (69%; 51/74 vs. 31%; 23/74) ranging in size from 0.395 Mb to 10.676 Mb (microdeletions) and 0.544 Mb to 8.156 Mb (microduplications), but their sizes were not significantly different (P = 0.83). The pathogenic/likely pathogenic CNVs (median 2.663 Mb) were significantly larger than benign CNVs (median 0.394 Mb) (P
Databáze: OpenAIRE
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