Rare renal ciliopathies in non-consanguineous families that were identified by targeted resequencing.
Rare renal ciliopathies in non-consanguineous families that were identified by targeted resequencing.
复制标题
通过靶向重测序发现的非近亲家庭中罕见的肾纤毛病。
DOI：
10.1007/s10157-016-1256-x
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Iijima K.
中科院分区：
文献类型：
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作者：
Yamamura T;Morisada N;Nozu K;Minamikawa S;Ishimori S;Toyoshima D;Ninchoji T;Yasui M;Taniguchi-Ikeda M;Morioka I;Nakanishi K;Nishio H;Iijima K.
肾病相关性纤毛病变（NPHP-RC）是儿童和青少年肾功能衰竭的常见原因。虽然诊断这些疾病临床上是困难的，一个全面的遗传筛查方法，有针对性的重测序可以发现在这个复杂的家庭diseases.MethodsWe研究了三个日本女性患者肾功能不全，从非血缘的父母的遗传背景。由于临床原因，未进行肾活检。因此，我们无法从临床方面了解这些患者的诊断。我们使用TruSight One Sequencing Panel下一代测序技术进行了全面的遗传分析。ResultsWe在以下基因中鉴定了三种不同的罕见NPHP-RC变体：SDCCAG 8，MKKS和WDR 35。SDCCAG 8纯合子缺失的患者1在基因分析前未表现出睫状体病特异性肾外表现，如视网膜色素变性或多指（趾）畸形。患者2具有aMKKS剪接位点纯合突变和随后在底物结合顶端结构域中的39个氨基酸缺失，具有Bardet-Biedl综合征的临床症状。她和她已故的哥哥出生后不久就有严重的肾功能不全。患者3与一个复合heteroadherousWDR 35 mutation有眼缺损和智力disability.ConclusionsOur研究结果表明，一个全面的基因筛查系统，使用目标重测序是有用的，非侵入性的诊断原因不明的儿童终末期肾病患者。
BackgroundNephronophthisis-related ciliopathies (NPHP-RC) are a frequent cause of renal failure for children and adolescents. Although diagnosing these diseases clinically is difficult, a comprehensive genetic screening approach of targeted resequencing can uncover the genetic background in this complicated family of diseases.MethodsWe studied three Japanese female patients with renal insufficiency from non-consanguineous parents. A renal biopsy for clinical reasons was not performed. Therefore, we did not know the diagnosis of these patients from a clinical aspect. We performed comprehensive genetic analysis using the TruSight One Sequencing Panel next generation sequencing technique.ResultsWe identified three different rare NPHP-RC variants in the following genes:SDCCAG8,MKKS, andWDR35. Patient 1 withSDCCAG8homozygous deletions showed no ciliopathy-specific extrarenal manifestations, such as retinitis pigmentosa or polydactyly prior to genetic analysis. Patient 2 with aMKKSsplice site homozygous mutation and a subsequent 39-amino acid deletion in the substrate-binding apical domain, had clinical symptoms of Bardet–Biedl syndrome. She and her deceased elder brother had severe renal insufficiency soon after birth. Patient 3 with a compound heterozygousWDR35mutation had ocular coloboma and intellectual disability.ConclusionsOur results suggest that a comprehensive genetic screening system using target resequencing is useful and non-invasive for the diagnosis of patients with an unknown cause of pediatric end-stage renal disease.