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Erschienen in: Clinical and Experimental Nephrology 4/2018

25.01.2018 | Original article

Detection of copy number variations by pair analysis using next-generation sequencing data in inherited kidney diseases

verfasst von: 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

Erschienen in: Clinical and Experimental Nephrology | Ausgabe 4/2018

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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.
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Metadaten
Titel
Detection of copy number variations by pair analysis using next-generation sequencing data in inherited kidney diseases
verfasst von
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
Publikationsdatum
25.01.2018
Verlag
Springer Singapore
Erschienen in
Clinical and Experimental Nephrology / Ausgabe 4/2018
Print ISSN: 1342-1751
Elektronische ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-018-1534-x

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