title: Analysis of the genes responsible for steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis in Japanese patients by whole-exome sequencing analysis.
abstract: 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.
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ogino
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
authors.forename: Motoshi
authors.initials: M
authors.lastname: Hattori
authors.affiliation: Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sugawara
authors.affiliation: Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Akioka
authors.affiliation: Statistical Genetics and Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Tamiya
authors.affiliation: Statistical Genetics and Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Makino
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Toyota
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Mitsui
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.|Department of Pediatrics, Miyukikai Hospital, Kaminoyma, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D059472:Exome; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D009404:Nephrotic Syndrome / Q000150:complications / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D017422:Sequence Analysis, DNA; D055815:Young Adult