J 2021

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

ZECH, M., S. BOESCH, M. SKORVANEK, J. NECPAL, J. SVANTNEROVA et. al.

Basic information

Original name

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

Authors

ZECH, M. (guarantor), S. BOESCH, M. SKORVANEK, J. NECPAL, J. SVANTNEROVA, M. WAGNER, Y. DINCER, A. SADR-NABAVI, T. SERRANOVA, Irena REKTOROVÁ (203 Czech Republic, belonging to the institution), P. HAVRANKOVA (203 Czech Republic), S. GANAI, A. MOSEJOVA, I. PRIHODOVA (203 Czech Republic), J. SARLAKOVA (203 Czech Republic), K. KULCSAROVA, O. ULMANOVA (203 Czech Republic), K. BECHYNE, M. OSTROZOVICOVA, V. HAN, J. R. VENTOSA, M. SHARIATI, A. SHOEIBI, S. WEBER, B. MOLLENHAUER, C. TRENKWALDER, R. BERUTTI, T. M. STROM, A. CEBALLOS-BAUMANN, V. MALL, B. HASLINGER, R. JECH (203 Czech Republic) and J. WINKELMANN

Edition

PARKINSONISM & RELATED DISORDERS, OXFORD, ELSEVIER SCI LTD, 2021, 1353-8020

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30210 Clinical neurology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 4.402

RIV identification code

RIV/00216224:14110/21:00121363

Organization unit

Faculty of Medicine

UT WoS

000628766400001

Keywords in English

Copy-number variant; Dystonia; Read-depth analysis; Diagnostic yield

Tags

International impact, Reviewed
Změněno: 18/1/2022 09:40, Mgr. Tereza Miškechová

Abstract

V originále

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.

Links

825575, interní kód MU
Name: European Joint Programme on Rare Diseases (Acronym: EJP RD)
Investor: European Union, Health, demographic change and wellbeing (Societal Challenges)