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

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

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

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OECD FORD branch

30210 - Clinical neurology

Project

<a href="/en/project/NV19-04-00233" target="_blank" >NV19-04-00233: Clinical, Imaging and Biological predictors of effects associated with deep brain stimulation in Parkinson’s disease</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

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

Name of the periodical

Parkinsonism &amp; Related Disorders

ISSN

1353-8020

e-ISSN

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Volume of the periodical

84

Issue of the periodical within the volume

MAR 2021

Country of publishing house

US - UNITED STATES

Number of pages

6

Pages from-to

129-134

UT code for WoS article

000628766400001

EID of the result in the Scopus database

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