Detection of Copy Number Variations by Pair Analysis Using Next-generation Sequencing Data in Inherited Kidney Diseases

Overview

Journal Clin Exp Nephrol

Publisher Springer

Specialty Nephrology

Date 2018 Jan 27

PMID 29372472

Citations 15

Authors

China Nagano

Kandai Nozu

Naoya Morisada

Masahiko Yazawa

Daisuke Ichikawa

Keita Numasawa

Hiroyo Kourakata

Chieko Matsumura

Satoshi Tazoe

Ryojiro Tanaka

Tomohiko Yamamura

Shogo Minamikawa

Tomoko Horinouchi

Keita Nakanishi

Junya Fujimura

Nana Sakakibara

Yoshimi Nozu

Ming Juan Ye

Hiroshi Kaito

Kazumoto Iijima

Affiliations

Soon will be listed here.

Abstract

Background: Comprehensive genetic approaches for diagnosing inherited kidney diseases using next-generation sequencing (NGS) have recently been established. However, even with these approaches, we are still failing to detect gene defects in some patients who appear to suffer from genetic diseases. One of the reasons for this is the difficulty of detecting copy number variations (CNVs) using our current approaches. For such cases, we can apply methods of array-based comparative genomic hybridization (aCGH) or multiplex ligation and probe amplification (MLPA); however, these are expensive and laborious and also often fail to identify CNVs. Here, we report seven cases with CNVs in various inherited kidney diseases screened by NGS pair analysis.

Methods: Targeted sequencing analysis for causative genes was conducted for cases with suspected inherited kidney diseases, for some of which a definitive genetic diagnosis had not been achieved. We conducted pair analysis using NGS data for those cases. When CNVs were detected by pair analysis, they were confirmed by aCGH and/or MLPA.

Results: In seven cases, CNVs in various causative genes of inherited kidney diseases were detected by pair analysis. With aCGH and/or MLPA, pathogenic CNV variants were confirmed: COL4A5 or HNF1B in two cases each, and EYA1, CLCNKB, or PAX2 in one each.

Conclusion: We presented seven cases with CNVs in various genes that were screened by pair analysis. The NGS-based CNV detection method is useful for comprehensive screening of CNVs, and our results revealed that, for a certain proportion of cases, CNV analysis is necessary for accurate genetic diagnosis.

Citing Articles

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Copy number variation analysis in 138 families with steroid-resistant nephrotic syndrome identifies causal homozygous deletions in PLCE1 and NPHS2 in two families.

Pantel D, Mertens N, Schneider R, Holzel S, Kari J, El Desoky S Pediatr Nephrol. 2023; 39(2):455-461.

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The Contribution of Splicing Variants to the Pathogenesis of X-Linked Alport Syndrome.

Yamamura T, Horinouchi T, Aoto Y, Lennon R, Nozu K Front Med (Lausanne). 2022; 9:841391.

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Clinical features of autosomal recessive polycystic kidney disease in the Japanese population and analysis of splicing in PKHD1 gene for determination of phenotypes.

Ishiko S, Morisada N, Kondo A, Nagai S, Aoto Y, Okada E Clin Exp Nephrol. 2021; 26(2):140-153.

PMID: 34536170 PMC: 8770369. DOI: 10.1007/s10157-021-02135-3.

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