Ogino Daisuke, Hashimoto Taeko, Hattori Motoshi, Sugawara Noriko, Akioka Yuko, Tamiya Gen, Makino Satoshi, Toyota Kentaro, Mitsui Tetsuo, Hayasaka Kiyoshi
Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
J Hum Genet. 2016 Feb;61(2):137-41. doi: 10.1038/jhg.2015.122. Epub 2015 Oct 15.
Steroid-resistant nephrotic syndrome (SRNS) represents glomerular disease resulting from a number of different etiologies leading to focal segmental glomerulosclerosis (FSGS). Recently, many genes causing SRNS/FSGS have been identified. These genes encode the proteins associated with the formation and/or maintenance of glomerular filtration barrier. Next-generation sequencing is used to analyze large numbers of genes at lower costs. To identify the genetic background of Japanese patients, we studied 26 disease-causing genes using whole-exome sequencing analysis in 24 patients with SRNS and/or FSGS from 22 different Japanese families. We finally found eight causative gene mutations, four recessive and four dominant gene mutations, including three novel mutations, in six patients from five different families, and one novel predisposing mutation in two patients from two different families. Causative gene mutations have only been identified in ~20% of families and further analysis is necessary to identify the unknown disease-causing gene. Identification of the disease-causing gene would support clinical practices, including the diagnosis, understanding of pathogenesis and treatment.
类固醇抵抗型肾病综合征（SRNS）是由多种不同病因导致的肾小球疾病，可引发局灶节段性肾小球硬化（FSGS）。近来，许多导致SRNS/FSGS的基因已被鉴定出来。这些基因编码与肾小球滤过屏障的形成和/或维持相关的蛋白质。新一代测序技术能够以更低的成本分析大量基因。为了确定日本患者的遗传背景，我们对来自22个不同日本家庭的24例SRNS和/或FSGS患者进行全外显子测序分析，研究了26个致病基因。我们最终在来自5个不同家庭的6例患者中发现了8个致病基因突变，其中4个为隐性突变，4个为显性基因突变，包括3个新突变；在来自2个不同家庭的2例患者中发现了1个新的易感突变。仅在约20%的家庭中鉴定出了致病基因突变，因此需要进一步分析以确定未知的致病基因。致病基因的鉴定将有助于临床实践，包括诊断、发病机制的理解和治疗。
