Pair analysis and custom array CGH can detect a small copy number variation in COQ6 gene
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Recently, comprehensive genetic approaches for steroid-resistant nephrotic syndrome (SRNS) using next-generation sequencing (NGS) have been established, but causative gene mutations could not be detected in almost 70% of SRNS patients. Main reason for the low variant detection rate is that most of them are SRNS caused not by genetic but by immunological factors. But some of them are probably because of the difficulty of detecting copy number variations (CNVs) in causative genes by NGS.
In this study, we performed two analytical methods of NGS data-dependent pair analysis and custom array comparative genomic hybridization (aCGH) in addition to NGS analysis in an infantile nephrotic syndrome case.
We detected only one known pathogenic heterozygous missense mutation in exon 7 of COQ6 c.782C > T, p.(Pro261Leu) by NGS. With pair analysis, heterozygous exon 1–2 deletion was suspected and was confirmed by custom aCGH. As a result, a small CNV was successfully detected in the COQ6 gene. Because we could detect variants in COQ6 and could start treatment by coenzyme Q10 (CoQ10) in his very early stage of SRNS, the patient achieved complete remission.
These relatively novel methods should be adopted in cases with negative results in gene tests by NGS analysis. Especially, in cases with CoQ10 deficiency, it is possible to delay initiating dialysis by starting treatment at their early stages.
KeywordsCOQ6 CoQ10 glomerulopathy Copy number variation Pair analysis Custom array comparative genomic hybridization
This study was supported by a Grant from the Ministry of Health, Labour and Welfare of Japan for Research on Rare Intractable Diseases in the Kidney and Urinary Tract [H24-nanchitou (nan)-ippan-041 to Kazumoto Iijima] in the “Research on Measures for Intractable Diseases” Project; Grants-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (subject ID: 17K16262 to Keita Nakanishi, 15K09691 to Kandai Nozu, and 17H04189 to Kazumoto Iijima); and by Japan Agency for Medical Research and Development AMED under Grant number 7930006 to Kandai Nozu and Kazumoto Iijima. We thank Edanz Group (http://www.edanzediting.com/ac) for editing a draft of this manuscript.
Compliance with ethical standards
Conflict of interest
The authors have nothing to disclose.
All procedures were reviewed and approved by the Institutional Review Board of Kobe University School of Medicine.
Informed consent was obtained from the patient’s parents.
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