Biallelic structural variants in three patients with ERCC8-related Cockayne syndrome and a potential pitfall of copy number variation analysis.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
26 08 2024
26 08 2024
Historique:
received:
31
01
2024
accepted:
21
08
2024
medline:
27
8
2024
pubmed:
27
8
2024
entrez:
26
8
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39187681
doi: 10.1038/s41598-024-70831-7
pii: 10.1038/s41598-024-70831-7
doi:
Substances chimiques
ERCC8 protein, human
0
DNA Repair Enzymes
EC 6.5.1.-
Transcription Factors
0
Types de publication
Journal Article
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
19741Subventions
Organisme : Japan Society for the Promotion of Science
ID : 20K08236
Organisme : Japan Society for the Promotion of Science
ID : 20H03646
Organisme : Japan Agency for Medical Research and Development
ID : JP23ek0109549
Informations de copyright
© 2024. The Author(s).
Références
Cockayne, E. A. Dwarfism with retinal atrophy and deafness. Arch. Dis. Child 11, 1–8. https://doi.org/10.1136/adc.11.61.1 (1936).
doi: 10.1136/adc.11.61.1
pubmed: 21032019
pmcid: 1975412
Laugel, V. et al. Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. Hum. Mutat. 31, 113–126. https://doi.org/10.1002/humu.21154 (2010).
doi: 10.1002/humu.21154
pubmed: 19894250
Nance, M. A. & Berry, S. A. Cockayne syndrome: Review of 140 cases. Am. J. Med. Genet. 42, 68–84. https://doi.org/10.1002/ajmg.1320420115 (1992).
doi: 10.1002/ajmg.1320420115
pubmed: 1308368
de Boer, J. & Hoeijmakers, J. H. Nucleotide excision repair and human syndromes. Carcinogenesis 21, 453–460. https://doi.org/10.1093/carcin/21.3.453 (2000).
doi: 10.1093/carcin/21.3.453
pubmed: 10688865
Duan, J., Zhang, J. G., Deng, H. W. & Wang, Y. P. CNV-TV: A robust method to discover copy number variation from short sequencing reads. BMC Bioinform. 14, 150. https://doi.org/10.1186/1471-2105-14-150 (2013).
doi: 10.1186/1471-2105-14-150
Ceulemans, S., van der Ven, K. & Del-Favero, J. Targeted screening and validation of copy number variations. Methods Mol. Biol. 838, 311–328. https://doi.org/10.1007/978-1-61779-507-7_15 (2012).
doi: 10.1007/978-1-61779-507-7_15
pubmed: 22228019
Plagnol, V. et al. A robust model for read count data in exome sequencing experiments and implications for copy number variant calling. Bioinformatics 28, 2747–2754. https://doi.org/10.1093/bioinformatics/bts526 (2012).
doi: 10.1093/bioinformatics/bts526
pubmed: 22942019
pmcid: 3476336
Fromer, M. et al. Discovery and statistical genotyping of copy-number variation from whole-exome sequencing depth. Am. J. Hum. Genet. 91, 597–607. https://doi.org/10.1016/j.ajhg.2012.08.005 (2012).
doi: 10.1016/j.ajhg.2012.08.005
pubmed: 23040492
pmcid: 3484655
Jiang, Y. et al. CODEX2: Full-spectrum copy number variation detection by high-throughput DNA sequencing. Genome Biol. 19, 202. https://doi.org/10.1186/s13059-018-1578-y (2018).
doi: 10.1186/s13059-018-1578-y
pubmed: 30477554
pmcid: 6260772
D’Aurizio, R. et al. Enhanced copy number variants detection from whole-exome sequencing data using EXCAVATOR2. Nucleic Acids Res. 44, e154. https://doi.org/10.1093/nar/gkw695 (2016).
doi: 10.1093/nar/gkw695
pubmed: 27507884
pmcid: 5175347
Gordeeva, V. et al. Benchmarking germline CNV calling tools from exome sequencing data. Sci. Rep. 11, 14416. https://doi.org/10.1038/s41598-021-93878-2 (2021).
doi: 10.1038/s41598-021-93878-2
pubmed: 34257369
pmcid: 8277855
Tan, R. et al. An evaluation of copy number variation detection tools from whole-exome sequencing data. Hum. Mutat. 35, 899–907. https://doi.org/10.1002/humu.22537 (2014).
doi: 10.1002/humu.22537
pubmed: 24599517
Samarakoon, P. S. et al. Identification of copy number variants from exome sequence data. BMC Genom. 15, 661. https://doi.org/10.1186/1471-2164-15-661 (2014).
doi: 10.1186/1471-2164-15-661
Hong, C. S., Singh, L. N., Mullikin, J. C. & Biesecker, L. G. Assessing the reproducibility of exome copy number variations predictions. Genome Med. 8, 82. https://doi.org/10.1186/s13073-016-0336-6 (2016).
doi: 10.1186/s13073-016-0336-6
pubmed: 27503473
pmcid: 4976506
Yao, R. et al. Evaluation of three read-depth based CNV detection tools using whole-exome sequencing data. Mol. Cytogenet. 10, 30. https://doi.org/10.1186/s13039-017-0333-5 (2017).
doi: 10.1186/s13039-017-0333-5
pubmed: 28852425
pmcid: 5569469
Zhao, L., Liu, H., Yuan, X., Gao, K. & Duan, J. Comparative study of whole exome sequencing-based copy number variation detection tools. BMC Bioinform. 21, 97. https://doi.org/10.1186/s12859-020-3421-1 (2020).
doi: 10.1186/s12859-020-3421-1
Uchiyama, Y. et al. Efficient detection of copy-number variations using exome data: Batch- and sex-based analyses. Hum. Mutat. 42, 50–65. https://doi.org/10.1002/humu.24129 (2021).
doi: 10.1002/humu.24129
pubmed: 33131168
Miya, F. et al. A combination of targeted enrichment methodologies for whole-exome sequencing reveals novel pathogenic mutations. Sci. Rep. 5, 9331. https://doi.org/10.1038/srep09331 (2015).
doi: 10.1038/srep09331
pubmed: 25786579
pmcid: 4365396
Suzuki, H., Yamada, M., Uehara, T., Takenouchi, T. & Kosaki, K. Parallel detection of single nucleotide variants and copy number variants with exome analysis: Validation in a cohort of 700 undiagnosed patients. Am. J. Med. Genet. A 182, 2529–2532. https://doi.org/10.1002/ajmg.a.61822 (2020).
doi: 10.1002/ajmg.a.61822
pubmed: 32779332
pmcid: 7689761
Zook, J. M. et al. A robust benchmark for detection of germline large deletions and insertions. Nat. Biotechnol. 38, 1347–1355. https://doi.org/10.1038/s41587-020-0538-8 (2020).
doi: 10.1038/s41587-020-0538-8
pubmed: 32541955
pmcid: 8454654
Janssen, R. J. et al. Contiguous gene deletion of ELOVL7, ERCC8 and NDUFAF2 in a patient with a fatal multisystem disorder. Hum. Mol. Genet. 18, 3365–3374. https://doi.org/10.1093/hmg/ddp276 (2009).
doi: 10.1093/hmg/ddp276
pubmed: 19525295
Ren, Y. et al. Three novel mutations responsible for Cockayne syndrome group A. Genes Genet. Syst. 78, 93–102. https://doi.org/10.1266/ggs.78.93 (2003).
doi: 10.1266/ggs.78.93
pubmed: 12655141
Ting, T. W. et al. Cockayne Syndrome due to a maternally-inherited whole gene deletion of ERCC8 and a paternally-inherited ERCC8 exon 4 deletion. Gene 572, 274–278. https://doi.org/10.1016/j.gene.2015.07.065 (2015).
doi: 10.1016/j.gene.2015.07.065
pubmed: 26210811
Wang, X. et al. Molecular spectrum of excision repair cross-complementation group 8 gene defects in Chinese patients with Cockayne syndrome type A. Sci. Rep. 7, 13686. https://doi.org/10.1038/s41598-017-14034-3 (2017).
doi: 10.1038/s41598-017-14034-3
pubmed: 29057985
pmcid: 5651726
Xie, H. et al. A complex intragenic rearrangement of ERCC8 in Chinese siblings with Cockayne syndrome. Sci. Rep. 7, 44271. https://doi.org/10.1038/srep44271 (2017).
doi: 10.1038/srep44271
pubmed: 28333167
pmcid: 5363064
Calmels, N. et al. Functional and clinical relevance of novel mutations in a large cohort of patients with Cockayne syndrome. J. Med. Genet. 55, 329–343. https://doi.org/10.1136/jmedgenet-2017-104877 (2018).
doi: 10.1136/jmedgenet-2017-104877
pubmed: 29572252
Cloney, T. et al. Lessons learnt from multifaceted diagnostic approaches to the first 150 families in Victoria’s Undiagnosed Diseases Program. J. Med. Genet. 59, 748–758. https://doi.org/10.1136/jmedgenet-2021-107902 (2022).
doi: 10.1136/jmedgenet-2021-107902
pubmed: 34740920
Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760. https://doi.org/10.1093/bioinformatics/btp324 (2009).
doi: 10.1093/bioinformatics/btp324
pubmed: 19451168
pmcid: 2705234
McKenna, A. et al. The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303. https://doi.org/10.1101/gr.107524.110 (2010).
doi: 10.1101/gr.107524.110
pubmed: 20644199
pmcid: 2928508
San-Lucas, F. A., Wang, G., Scheet, P. & Peng, B. Integrated annotation and analysis of genetic variants from next-generation sequencing studies with variant tools. Bioinformatics 28, 421–422. https://doi.org/10.1093/bioinformatics/btr667 (2012).
doi: 10.1093/bioinformatics/btr667
pubmed: 22138362
Tadaka, S. et al. jMorp: Japanese Multi-Omics Reference Panel update report 2023. Nucleic Acids Res. https://doi.org/10.1093/nar/gkad978 (2023).
doi: 10.1093/nar/gkad978
pmcid: 10767895