Detailed Information on Publication Record
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 |
|