Clinically relevant copy-number variants in exome sequencing data of patients with dystonia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F21%3A00074711" target="_blank" >RIV/00159816:_____/21:00074711 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/21:10425827 RIV/00179906:_____/21:10425827 RIV/00064165:_____/21:10425827 RIV/00216224:14110/21:00121363

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S1353802021000547?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S1353802021000547?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.parkreldis.2021.02.013" target="_blank" >10.1016/j.parkreldis.2021.02.013</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Clinically relevant copy-number variants in exome sequencing data of patients with dystonia

Popis výsledku v původním jazyce

Introduction: Next-generation sequencing is now used on a routine basis for molecular testing but studies on copy-number variant (CNV) detection from next-generation sequencing data are underrepresented. Utilizing an existing whole-exome sequencing (WES) dataset, we sought to investigate the contribution of rare CNVs to the genetic causality of dystonia. Methods: The CNV read-depth analysis tool ExomeDepth was applied to the exome sequences of 953 unrelated patients with dystonia (600 with isolated dystonia and 353 with combined dystonia; 33% with additional neurological involvement). We prioritized rare CNVs that affected known disease genes and/or were known to be associated with defined microdeletion/microduplication syndromes. Pathogenicity assessment of CNVs was based on recently published standards of the American College of Medical Genetics and Genomics and the Clinical Genome Resource. Results: We identified pathogenic or likely pathogenic CNVs in 14 of 953 patients (1.5%). Of the 14 different CNVs, 12 were deletions and 2 were duplications, ranging in predicted size from 124bp to 17 Mb. Within the deletion intervals, BRPF1, CHD8, DJ1, EFTUD2, FGF14, GCH1, PANK2, SGCE, UBE3A, VPS16, WARS2, and WDR45 were determined as the most clinically relevant genes. The duplications involved chromosomal regions 6q21-q22 and 15q11-q13. CNV analysis increased the diagnostic yield in the total cohort from 18.4% to 19.8%, as compared to the assessment of single-nucleotide variants and small insertions and deletions alone. Conclusions: WES-based CNV analysis in dystonia is feasible, increases the diagnostic yield, and should be combined with the assessment of single-nucleotide variants and small insertions and deletions.

Název v anglickém jazyce

Clinically relevant copy-number variants in exome sequencing data of patients with dystonia

Popis výsledku anglicky

Introduction: Next-generation sequencing is now used on a routine basis for molecular testing but studies on copy-number variant (CNV) detection from next-generation sequencing data are underrepresented. Utilizing an existing whole-exome sequencing (WES) dataset, we sought to investigate the contribution of rare CNVs to the genetic causality of dystonia. Methods: The CNV read-depth analysis tool ExomeDepth was applied to the exome sequences of 953 unrelated patients with dystonia (600 with isolated dystonia and 353 with combined dystonia; 33% with additional neurological involvement). We prioritized rare CNVs that affected known disease genes and/or were known to be associated with defined microdeletion/microduplication syndromes. Pathogenicity assessment of CNVs was based on recently published standards of the American College of Medical Genetics and Genomics and the Clinical Genome Resource. Results: We identified pathogenic or likely pathogenic CNVs in 14 of 953 patients (1.5%). Of the 14 different CNVs, 12 were deletions and 2 were duplications, ranging in predicted size from 124bp to 17 Mb. Within the deletion intervals, BRPF1, CHD8, DJ1, EFTUD2, FGF14, GCH1, PANK2, SGCE, UBE3A, VPS16, WARS2, and WDR45 were determined as the most clinically relevant genes. The duplications involved chromosomal regions 6q21-q22 and 15q11-q13. CNV analysis increased the diagnostic yield in the total cohort from 18.4% to 19.8%, as compared to the assessment of single-nucleotide variants and small insertions and deletions alone. Conclusions: WES-based CNV analysis in dystonia is feasible, increases the diagnostic yield, and should be combined with the assessment of single-nucleotide variants and small insertions and deletions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30210 - Clinical neurology

Projekt

<a href="/cs/project/NV19-04-00233" target="_blank" >NV19-04-00233: Klinické, zobrazovací a biologické prediktory účinků hluboké mozkové stimulace u Parkinsonovy nemoci</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Parkinsonism &amp; Related Disorders

ISSN

1353-8020

e-ISSN

—

Svazek periodika

84

Číslo periodika v rámci svazku

MAR 2021

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

6

Strana od-do

129-134

Kód UT WoS článku

000628766400001

EID výsledku v databázi Scopus

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