PMID- 31337399 OWN - NLM STAT- MEDLINE DCOM- 20200106 LR - 20200309 IS - 1755-8794 (Electronic) IS - 1755-8794 (Linking) VI - 12 IP - 1 DP - 2019 Jul 23 TI - The clinical benefit of array-based comparative genomic hybridization for detection of copy number variants in Czech children with intellectual disability and developmental delay. PG - 111 LID - 10.1186/s12920-019-0559-7 [doi] LID - 111 AB - 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 < 0.00001) and likewise the pathogenic/likely pathogenic CNVs (median 2.663 Mb) were significantly larger in size than VOUS (median 0.469 Mb) (P < 0.00001). CONCLUSIONS: Our results confirm the benefit of array-CGH in the current clinical genetic diagnostics leading to identification of the genetic cause of ID/DD in affected children. FAU - Wayhelova, Marketa AU - Wayhelova M AUID- ORCID: 0000-0003-0475-8890 AD - Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlarska 267/2, Brno, Czech Republic. marketa.wayhelova@mail.muni.cz. AD - Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, Brno, Czech Republic. marketa.wayhelova@mail.muni.cz. FAU - Smetana, Jan AU - Smetana J AD - Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlarska 267/2, Brno, Czech Republic. AD - Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, Brno, Czech Republic. FAU - Vallova, Vladimira AU - Vallova V AD - Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlarska 267/2, Brno, Czech Republic. AD - Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, Brno, Czech Republic. FAU - Hladilkova, Eva AU - Hladilkova E AD - Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, Brno, Czech Republic. FAU - Filkova, Hana AU - Filkova H AD - Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, Brno, Czech Republic. FAU - Hanakova, Marta AU - Hanakova M AD - Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, Brno, Czech Republic. FAU - Vilemova, Marcela AU - Vilemova M AD - Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, Brno, Czech Republic. FAU - Nikolova, Petra AU - Nikolova P AD - Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, Brno, Czech Republic. FAU - Gromesova, Barbora AU - Gromesova B AD - Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, Brno, Czech Republic. FAU - Gaillyova, Renata AU - Gaillyova R AD - Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, Brno, Czech Republic. FAU - Kuglik, Petr AU - Kuglik P AD - Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlarska 267/2, Brno, Czech Republic. AD - Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, Brno, Czech Republic. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190723 PL - England TA - BMC Med Genomics JT - BMC medical genomics JID - 101319628 SB - IM MH - Adolescent MH - Child MH - Child, Preschool MH - Cohort Studies MH - *Comparative Genomic Hybridization MH - Czech Republic MH - *DNA Copy Number Variations MH - Developmental Disabilities/*genetics MH - Female MH - Humans MH - Infant MH - Infant, Newborn MH - Intellectual Disability/*genetics MH - Male MH - *Oligonucleotide Array Sequence Analysis PMC - PMC6651926 OTO - NOTNLM OT - Array-CGH OT - CNV OT - Developmental delay OT - Intellectual disability OT - Microdeletion OT - Microduplication COIS- The authors declare that they have no competing interests. EDAT- 2019/07/25 06:00 MHDA- 2020/01/07 06:00 PMCR- 2019/07/23 CRDT- 2019/07/25 06:00 PHST- 2018/09/05 00:00 [received] PHST- 2019/07/16 00:00 [accepted] PHST- 2019/07/25 06:00 [entrez] PHST- 2019/07/25 06:00 [pubmed] PHST- 2020/01/07 06:00 [medline] PHST- 2019/07/23 00:00 [pmc-release] AID - 10.1186/s12920-019-0559-7 [pii] AID - 559 [pii] AID - 10.1186/s12920-019-0559-7 [doi] PST - epublish SO - BMC Med Genomics. 2019 Jul 23;12(1):111. doi: 10.1186/s12920-019-0559-7.