Publication details
Whole-exome sequencing as an effective tool for the detection of DNA sequence and structural variants in the pathogenesis of neurodevelopmental disorders
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| Year of publication | 2021 |
| Type | Conference abstract |
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| Citation | |
| Description | With more than 50% diagnostic yield the whole-exome sequencing (WES) represents an effective and powerful tool to identify causes of neurodevelopmental disorders (NDDs) at the molecular level. We present our experience with WES as an effective tool for the detection of pathogenic sequence variants, copy-number variations (CNVs) and losses of heterozygosity (LOH) using the commercial kit Human Core Exome (Twist Biosciences) and Illumina NovaSeq 600. Our pilot study included 20 families (trios or quatros) of children with severe NDDs and associated congenital abnormalities. In the optimization step for CNV detection using read-depth approach we confirmed and specified all CNVs and LOH regions previously detected by array-CGH+SNP in 8 families. Mainly, we identified recurrent de novo pathogenic sequence variants in clinically relevant SHANK3, GRIN1 and NSD1 genes, novel de novo pathogenic variants in KDM1A, KMT2E and GNAI1 genes, and a pathogenic sequence variant in EDA gene of maternal origin. All clinically relevant findings were manually verified using Sanger sequencing and qPCR and interpreted using a multistep approach based on information in integrated databases of genomic variants, relevant scientific literature, and individual anamnesis. Our pilot results confirm WES as a first-tier diagnostic test in the genetic evaluation of children with NDDs. Supported by Ministry of Health of the Czech Republic, grant nr. NU20-07-00145. All rights reserved. |
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