Identification of novel genes for congenital anomalies of Kidney and urinary tract (CAKUT) by CNV analyses and development of comprehensive gene testing for CAKUT

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390240
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kobe University
• Principal Investigator: IIJIMA Kazumoto Kobe University, 大学院・医学研究科, 教授 (00240854)
• Co-Investigator(Kenkyū-buntansha): NAGATA Michio 筑波大学, 大学院・人間総合科学, 教授 (10192238)
• Co-Investigator(Renkei-kenkyūsha): NAKAYAMA Makioko 東北大学, 大学院・学系研究科, 大学院生 (80469999) ; MORISADA Naoya 神戸大学, 大学院・医学研究科, 助教 (00389446) ; NOZU Kandai 神戸大学, 医学部附属病院, 助教 (70362796) ; HASHIMURA Yuya 神戸大学, 大学院・医学研究科, 助教 (80457077)
• Project Period (FY): 2008 – 2010
• Keywords: 先天性腎尿路奇形 / CNV解析 / 原因遺伝子

Research Abstract

Copy number variation (CNV) of human genome is associated with several diseases including congenital anomalies. To identify new genes responsible for congenital anomalies of kidney and urinary tract (CAKUT), we utilized Agilent genome-wide CNV 400k array. We identified 4 CNV regions, which were not detected in healthy controls and CNV databases. We found 8 genes within or around these CNV regions. Of these genes, we identified a gene in which a CAKUT-specific heterozygous deletion resulted in deletion of 3 exons. We will analyze whether these genes are responsible for CAKUT. We developed comprehensive gene testing systems for known CAKUT genes (HNF1B, PAX2, EYA1, SIX1, SALL1) using multiplex ligation-dependent probe amplification and mRNA level analysis as well as direct sequencing of genomic DNA.

Research Products

• [Journal Article] Recurrent Deep Intronic Mutations in the SLC12A3 Gene Responsible for Gitelman's Syndrome. (2011)
  • Author(s): Lo YF, Nozu K, Iijima K, Morishita T, Huang CC, Yang SS, Sytwu HK, Fang YW, Tseng MH, Lin SH.
  • Journal Title: Clin J Am Soc Nephrol. 6(3) Pages: 630-639
• [Journal Article] The Pharmacological Characteristics of Molecular-Based Inherited Salt-Losing Tubulopathies. (2010)
  • Author(s): Nozu K, Iijima K, Kanda K, Nakanishi K, Yoshikawa N, Satomura K, Kaito H, Hashimura Y, Ninchoji T, Komatsu H, Kamei K, Miyashita R, Kugo M, Ohashi H, Yamazaki H, Mabe H, Otsubo A, Igarashi T, Matsuo M.
  • Journal Title: J Clin Endocrinol Metab. 95(12) Pages: E511-518
• [Journal Article] Severe Alport syndrome in a young woman caused by a t(X;1)(q22.3;p36.32) balanced translocation. (2010)
  • Author(s): Iijima K, Nozu K, Kamei K, Nakayama M, Ito S, Matsuoka K, Ogata T, Kaito H, Nakanishi K, Matsuo M.
  • Journal Title: Pediatr Nephrol. 25(10) Pages: 2165-2170
• [Journal Article] HNF1B Alterations Associated with Congenital Anomalies of the Kidney and Urinary Tract. (2010)
  • Author(s): Nakayama M, Nozu K, Goto Y, Kamei K, Ito S, Sato H, Emi M, Nakanishi K, Tuchiya S, Iijima K.
  • Journal Title: Pediatr Nephrol 25(6) Pages: 1073-1079
• [Journal Article] Branchio-oto-renal syndrome caused by partial EYA1 deletion due to LINE-1 insertion. (2010)
  • Author(s): Morisada N, Rendtorff ND, Nozu K, Morishita T, Miyakawa T, Matsumoto T, Hisano S, Iijima K, Tranebjarg L, Shirahata A, Matsuo M, Kusuhara K.
  • Journal Title: Pediatr Nephrol 25(7) Pages: 1343-1348
• [Journal Article] Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene. (2009)
  • Author(s): Kanda K, Nozu K, Yokoyama N, Morioka I, Miwa A, Hashimura Y, Kaito H, Iijima K, Matsuo M.
  • Journal Title: BMC Nephrol 14 Pages: 10-37
• [Journal Article] A deep intronic mutation in the SLC12A3 gene leads to Gitelman syndrome. (2009)
  • Author(s): Nozu K, Iijima K, Nozu Y, Ikegami E, Imai T, Fu XJ, Kaito H, Nakanishi K, Yoshikawa N, Matsuo M.
  • Journal Title: Pediatr Res 66(5) Pages: 590-593
• [Journal Article] In vivo and in vitro splicing assay of SLC12A1 in an antenatal salt-losing tubulopathy patient with an intronic mutation. (2009)
  • Author(s): Nozu K, Iijima K, Kawai K, Nozu Y, Nishida A, Takeshima Y, Fu XJ, Hashimura Y, Kaito H, Nakanishi K, Yoshikawa N, Matsuo M.
  • Journal Title: Hum Genet 126(4) Pages: 533-538
• [Journal Article] Minimal change nephrotic syndrome associated with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. (2009)
  • Author(s): Hashimura Y, Nozu K, Kanegane H, Miyawaki T, Hayakawa A, Yoshikawa N, Nakanishi K, Takemoto M, Iijima K, Matsuo M.
  • Journal Title: Pediatr Nephrol 24(6) Pages: 1181-1186
• [Journal Article] Atypical phenotype of type I Bartter syndrome accompanied by focal segmental glomerulosclerosis. (2009)
  • Author(s): Yamazaki H, Nozu K, Narita I, Nagata M, Nozu Y, Fu XJ, Matsuo M, Iijima K, Gejyo F.
  • Journal Title: Pediatr Nephrol 24(2) Pages: 415-418
• [Journal Article] Steroid-resistant nephrotic syndrome. (2008)
  • Author(s): Kitamura A, Tsukaguchi H, Maruyama K, Shono A, Iijima K, Kagami S, Doi T.
  • Journal Title: Kidney Int. 74(9) Pages: 1209-1215
• [Journal Article] Detection of large deletion mutations in the COL4A5 gene of female Alport syndrome patients. (2008)
  • Author(s): Nozu K, Przybyslaw Krol R, Ohtsuka Y, Nakanishi K, Yoshikawa N, Nozu Y, Kaito H, Kanda K, Hashimura Y, Hamasaki Y, Iijima K, Matsuo M.
  • Journal Title: Pediatr Nephrol. 23(11) Pages: 2085-2090
• [Journal Article] Somatic mosaicism for a mutation of the COL4A5 gene is a cause of mild phenotype male Alport syndrome. (2008)
  • Author(s): Krol RP, Nozu K, Nakanishi K, Iijima K, Takeshima Y, Fu XJ, Nozu Y, Kaito H, Kanda K, Matsuo M, Yoshikawa N.
  • Journal Title: Nephrol Dial Transplant. 23(8) Pages: 2525-3250
• [Presentation] 「CAKUTに対する治療戦略」CAKUTと遺伝子変異 (2010)
  • Author(s): 飯島一誠, 野津寛大, 中山真紀子
  • Organizer: 第32回日本小児腎不全学会学術集会
  • Year and Date: 20100000
• [Presentation] Clinical and Immunohistochemical Analyses of Japanese Families with Genetically-Defined Autosomal-Recessive Alport Syndrome. (2010)
  • Author(s): Iijima K, Oka M, Hashimura Y, Ohtsuka Y, Kaito H, Sado Y, Yan K, Nakanishi K, Yoshikawa N, Nagasako H, Nozu K, Matsuo M.
  • Organizer: American Society of Nephrology 2010 Annual Meeting
  • Year and Date: 20100000
• [Presentation] A Deep Intronic Mutation in the SLC12A3 Gene leads to Gitelman Syndrome. (2009)
  • Author(s): Nozu K, Iijima K, Kaito H, Hashimura Y, Ninchoji T, Nakanishi K, Yoshikawa N, Matsuo M.
  • Organizer: American Society of Nephrology 2009 Annual Meeting
  • Year and Date: 20090000
• [Presentation] TCF2 Mutation in Patients with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). (2008)
  • Author(s): Nakayama M, Nozu K, Goto Y, Kamei K, Sato H, Emi M, Iijima K
  • Organizer: American Society of Nephrology 2008 Annual Meeting
  • Year and Date: 20080000
• [Presentation] The First Case of Minimal Change Nephrotic Syndrome Associated with Immunodysregulation, Polyendocrinopathy, Enteropathy, X-Linked (IPEX) Syndrome. (2008)
  • Author(s): Hashimura Y, Nozu K, Kanda K, Takeshima Y, Hayakawa A, Iijima K, Matsuo M.
  • Organizer: American Society of Nephrology 2008 Annual Meeting
  • Year and Date: 20080000
• [Book] Annual Review腎臓2010小児科領域TCF2遺伝子異常と先天性腎尿路奇形.(御手洗哲也, 東原英二, 秋澤忠男, 五十嵐隆, 金井好克編) (2010)
  • Author(s): 中山真紀子, 野津寛大, 飯島一誠
  • Total Pages: 212-218
  • Publisher: 中外医学社