Pair analysis and custom array CGH can detect a small copy number variation in COQ6 gene
Pair analysis and custom array CGH can detect a small copy number variation in COQ6 gene
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DOI：
10.1007/s10157-018-1682-z
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发表时间：
2019-05-01
影响因子：
2.3
通讯作者：
Iijima, Kazumoto
中科院分区：
文献类型：
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作者：
Nakanishi, Keita;Okamoto, Takayuki;Iijima, Kazumoto
背景：最近，使用下一代测序技术(NGS)对激素抵抗型肾病综合征(SRNS)进行基因检测的方法已经建立，但在几乎70%的SRNS患者中无法检测到致病基因突变。变异检出率低的主要原因是大多数SRN不是由遗传因素引起的，而是由免疫因素引起的。结果：在1例婴幼儿肾病综合征患儿中，仅检测到1例COQ6 c.782C>；T外显子7(Pro261Leu)已知的致病杂合错义突变。通过配对分析，怀疑外显子1-2杂合性缺失，并被定制的aCGH证实。结果，在COQ6基因中成功检测到一个小的CNV。由于我们可以检测到COQ6的变异，并在患者的SRNS早期就可以开始辅酶Q10(CoQ10)的治疗，患者获得了完全缓解。结论：对于NGS分析基因检测结果为阴性的病例，应采用这些相对新颖的方法。特别是在辅酶Q10缺乏的情况下，可以通过在早期阶段开始治疗来推迟开始透析。
Background: 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.Methods: 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.Results: 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.Conclusions: 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.