Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F24%3A00079464" target="_blank" >RIV/65269705:_____/24:00079464 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/24:10475840 RIV/00216224:14310/24:00139930

Result on the web

<a href="https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03056-6" target="_blank" >https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03056-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13023-024-03056-6" target="_blank" >10.1186/s13023-024-03056-6</a>

Result language

angličtina

Original language name

Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders

Original language description

BackgroundNeurodevelopmental disorders (NDDs) and/or associated multiple congenital abnormalities (MCAs) represent a genetically heterogeneous group of conditions with an adverse prognosis for the quality of intellectual and social abilities and common daily functioning. The rapid development of exome sequencing (ES) techniques, together with trio-based analysis, nowadays leads to up to 50% diagnostic yield. Therefore, it is considered as the state-of-the-art approach in these diagnoses.ResultsIn our study, we present the results of ES in a cohort of 85 families with 90 children with severe NDDs and MCAs. The interconnection of the in-house bioinformatic pipeline and a unique algorithm for variant prioritization resulted in a diagnostic yield of up to 48.9% (44/90), including rare and novel causative variants (41/90) and intragenic copy-number variations (CNVs) (3/90). Of the total number of 47 causative variants, 53.2% (25/47) were novel, highlighting the clinical benefit of ES for unexplained NDDs. Moreover, trio-based ES was verified as a reliable tool for the detection of rare CNVs, ranging from intragenic exon deletions (GRIN2A, ZC4H2 genes) to a 6-Mb duplication. The functional analysis using PANTHER Gene Ontology confirmed the involvement of genes with causative variants in a wide spectrum of developmental processes and molecular pathways, which form essential structural and functional components of the central nervous system.ConclusionTaken together, we present one of the first ES studies of this scale from the central European region. Based on the high diagnostic yield for paediatric NDDs in this study, 48.9%, we confirm trio-based ES as an effective and reliable first-tier diagnostic test in the genetic evaluation of children with NDDs.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10603 - Genetics and heredity (medical genetics to be 3)

Project

<a href="/en/project/NU20-07-00145" target="_blank" >NU20-07-00145: The role of pathogenic genetic variants identified by exome sequencing in the etiology of pediatric neurodevelopmental disorders</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Orphanet Journal of Rare Diseases

ISSN

1750-1172

e-ISSN

1750-1172

Volume of the periodical

19

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

41

UT code for WoS article

001158382600001

EID of the result in the Scopus database

2-s2.0-85184465431