Biallelic structural variants in three patients with ERCC8-related Cockayne syndrome and a potential pitfall of copy number variation analysis

Cockayne syndrome (CS) is a rare autosomal recessive disorder caused by mutations in ERCC8 or ERCC6. Most pathogenic variants in ERCC8 are single nucleotide substitutions. Structural variants (SVs) have been reported in patients with ERCC8-related CS. However, comprehensive molecular detection, including SVs of ERCC8, in CS patients remains problematic. Herein, we present three Japanese patients with ERCC8-related CS in whom causative SVs were identified using whole-exome-based copy number variation (CNV) detection tools. One patient showed compound heterozygosity for a 259-kb deletion and a deletion of exon 4 which has previously been reported as an Asia-specific variant. The other two patients were homozygous for the same exon 4 deletion. The exon 4 deletion was detected only by the ExomeDepth software. Intrigued by the discrepancy in the detection capability of various tools for the SVs, we evaluated the analytic performance of four whole-exome-based CNV detection tools using an exome data set from 337 healthy individuals. A total of 1,278,141 exons were predicted as being affected by the 4 CNV tools. Interestingly 95.1% of these affected exons were detected by one tool alone. Thus, we expect that the use of multiple tools may improve the detection rate of SVs from aligned exome data.

Authors

Institutions

Publication Details

Journal
Scientific Reports
Published
2024-08-26
DOI
https://doi.org/10.1038/s41598-024-70831-7
Citations
5
Primary Topic
Genomic variations and chromosomal abnormalities
Type
article
Field-Weighted Citation Impact
2.75

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Biallelic structural variants in three patients with ERCC8-related Cockayne syndrome and a potential pitfall of copy number variation analysis

Yonehiro Kanemura, Shinji Saitoh, Nobuhiko Okamoto, Mamiko Yamada et al.
5 citations
Scientific Reports
Genomic variations and chromosomal abnormalities
2.75
article

Biallelic structural variants in three patients with ERCC8-related Cockayne syndrome and a potential pitfall of copy number variation analysis

Yonehiro Kanemura, Shinji Saitoh, Nobuhiko Okamoto, Mamiko Yamada, Daisuke Watanabe, Daisuke Nakato, Mitsuhiro Kato, Tatsuhiko Tsunoda, Fuyuki Miya, Toshiki Takenouchi, Hisato Suzuki, Yuichi Kobayashi, Kenjiro Kosaki, Masayuki Sato
article en
5 citations

Abstract

Cockayne syndrome (CS) is a rare autosomal recessive disorder caused by mutations in ERCC8 or ERCC6. Most pathogenic variants in ERCC8 are single nucleotide substitutions. Structural variants (SVs) have been reported in patients with ERCC8-related CS. However, comprehensive molecular detection, including SVs of ERCC8, in CS patients remains problematic. Herein, we present three Japanese patients with ERCC8-related CS in whom causative SVs were identified using whole-exome-based copy number variation (CNV) detection tools. One patient showed compound heterozygosity for a 259-kb deletion and a deletion of exon 4 which has previously been reported as an Asia-specific variant. The other two patients were homozygous for the same exon 4 deletion. The exon 4 deletion was detected only by the ExomeDepth software. Intrigued by the discrepancy in the detection capability of various tools for the SVs, we evaluated the analytic performance of four whole-exome-based CNV detection tools using an exome data set from 337 healthy individuals. A total of 1,278,141 exons were predicted as being affected by the 4 CNV tools. Interestingly 95.1% of these affected exons were detected by one tool alone. Thus, we expect that the use of multiple tools may improve the detection rate of SVs from aligned exome data.

Scientific ReportsVol. 14(1)
SHOWA Medical University (JP), Tokyo Medical and Dental University (JP), University of Tsukuba (JP), Keio University (JP), Nagoya City University (JP), Osaka National Hospital (JP), Osaka Women's and Children's Hospital (JP), Keio University Hospital (JP), RIKEN Center for Integrative Medical Sciences (JP), SHOWA Medical University Hospital (JP), University of Yamanashi (JP), The University of Tokyo (JP)
Japan Agency for Medical Research and Development, Japan Society for the Promotion of Science
Good health and well-being
Openalex Percentile: Top 10%
Genomic variations and chromosomal abnormalities
2.75
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.