Whole-exome sequencing as an effective tool for the detection
of DNA sequence and structural variants in the pathogenesis of
neurodevelopmental disorders

a 2021

Whole-exome sequencing as an effective tool for the detection of DNA sequence and structural variants in the pathogenesis of neurodevelopmental disorders

WAYHELOVÁ, Markéta, Vladimíra VALLOVÁ, Jan SMETANA, Petr BROŽ, Aneta MIKULÁŠOVÁ et. al.

Basic information

Original name

Whole-exome sequencing as an effective tool for the detection of DNA sequence and structural variants in the pathogenesis of neurodevelopmental disorders

Authors

WAYHELOVÁ, Markéta (203 Czech Republic, belonging to the institution), Vladimíra VALLOVÁ (703 Slovakia, belonging to the institution), Jan SMETANA (203 Czech Republic), Petr BROŽ (203 Czech Republic, belonging to the institution), Aneta MIKULÁŠOVÁ (203 Czech Republic, belonging to the institution), Dominika LOUBALOVÁ (203 Czech Republic, belonging to the institution), Renata GAILLYOVÁ (203 Czech Republic, belonging to the institution) and Petr KUGLÍK (203 Czech Republic, guarantor, belonging to the institution)

Edition

2021

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

10603 Genetics and heredity

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14310/21:00120208

Organization unit

Faculty of Science

Keywords in English

neurodevelopmental disorders; whole-exome sequencing; pathogenic sequence variants

Abstract

V originále

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.

Links

NU20-07-00145, research and development project

Name: Úloha patogenních genetických variant detekovaných pomocí exomového sekvenování v etiologii dětských neurovývojových onemocnění

Investor: Ministry of Health of the CR, Subprogram 1 - standard

Citovat

WAYHELOVÁ, Markéta, Vladimíra VALLOVÁ, Jan SMETANA, Petr BROŽ, Aneta MIKULÁŠOVÁ, Dominika LOUBALOVÁ, Renata GAILLYOVÁ and Petr KUGLÍK. Whole-exome sequencing as an effective tool for the detection of DNA sequence and structural variants in the pathogenesis of neurodevelopmental disorders. 2021.

@proceedings{1820678,
   author = {Wayhelová, Markéta and Vallová, Vladimíra and Smetana, Jan and Brož, Petr and Mikulášová, Aneta and Loubalová, Dominika and Gaillyová, Renata and Kuglík, Petr},
   keywords = {neurodevelopmental disorders; whole-exome sequencing; pathogenic sequence variants},
   language = {eng},
   title = {Whole-exome sequencing as an effective tool for the detection of DNA sequence and structural variants in the pathogenesis of neurodevelopmental disorders},
   year = {2021}
}

TY  - CONF
ID  - 1820678
AU  - Wayhelová, Markéta - Vallová, Vladimíra - Smetana, Jan - Brož, Petr - Mikulášová, Aneta - Loubalová, Dominika - Gaillyová, Renata - Kuglík, Petr
PY  - 2021
TI  - Whole-exome sequencing as an effective tool for the detection of DNA sequence and structural variants in the pathogenesis of neurodevelopmental disorders
KW  - neurodevelopmental disorders
KW  - whole-exome sequencing
KW  - pathogenic sequence variants
N2  - 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.
ER  -

WAYHELOVÁ, Markéta, Vladimíra VALLOVÁ, Jan SMETANA, Petr BROŽ, Aneta MIKULÁŠOVÁ, Dominika LOUBALOVÁ, Renata GAILLYOVÁ and Petr KUGLÍK. \textit{Whole-exome sequencing as an effective tool for the detection of DNA sequence and structural variants in the pathogenesis of neurodevelopmental disorders}. 2021.

Detailed Information on Publication Record