New responsible genes for CAKUT and development of comprehensive gene mutation detection system in CAKUT

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591192
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kobe University
• Principal Investigator: IIJIMA Kazumoto 神戸大学, 医学(系)研究科(研究院), 教授 (00240854)
• Co-Investigator(Kenkyū-buntansha): 長田 道夫 筑波大学, 人間総合科学研究科, 教授 (10192238)
• Project Period (FY): 2011 – 2013
• Keywords: 腎尿路奇形 / 原因遺伝子

Research Abstract

We utilized the genome-wide array CGH and the next generation sequencing to identify new responsible copy number variations or gene mutations. We found that deletions in the region of 1q21.1, 16q12.1q12.2, 16q12.1q13 and 8q12.1q12.3, and mutations of the UPK3A gene and EP300 gene may cause CAKUT. We also developed the comprehensive detection system of gene mutations and copy number variations responsible for CAKUT.

Research Products

• [Journal Article] Natural history of genetically proven autosomal recessive Alport syndrome (2014)
  • Author(s): Oka M, Nozu K, Kaito H, Fu XJ, Nakanishi K, Hashimura Y, Morisada N, Yan K, Matsuo M, Yoshikawa N, Vorechovsky I, Iijima K
  • Journal Title: Pediatr Nephrol Volume: (Epub ahead of print)
• [Journal Article] Rituximab treatment combined with methylprednisolone pulse therapy and immunosuppressants for childhood steroid-resistant nephrotic syndrome (2014)
  • Author(s): Kamei K, Okada M, Sato M, Fujimaru T, Ogura M, Nakayama M, Kaito H, Iijima K, Ito S
  • Journal Title: Pediatr Nephrol Volume: 29(7) Pages: 1181-7
• [Journal Article] The problem of transition from pediatric to adult healthcare in patients with steroid-sensitive nephrotic syndrome (SSNS): a survey of the experts (2014)
  • Author(s): Honda M, Iijima K, Ishikura K, Kaneko K
  • Journal Title: Clin Exp Nephrol Volume: (Epub ahead of print)
• [Journal Article] Milder clinical aspects of X-linked Alport syndrome in men positive for the collagen IVα5 chain (2014)
  • Author(s): Hashimura Y, Nozu K, Kaito H, Nakanishi K, Fu XJ, Ohtsubo H, Hashimoto F, Oka M, Ninchoji T, Ishimori S, Morisada N, Matsunoshita N, Kamiyoshi N, Yoshikawa N, Iijima K
  • Journal Title: Kidney Int. Volume: 85(5) Pages: 1208-13
• [Journal Article] Cyclosporine C2 monitoring for the treatment of frequently relapsing nephrotic syndrome in children : a multicenter randomized phase II trial (2014)
  • Author(s): Iijima K, Sako M, Oba MS, Ito S, Hataya H, Tanaka R, Ohwada Y, Kamei K, Ishikura K, Yata N, Nozu K, Honda M, Nakamura H, Nagata M, Ohashi Y, Nakanishi K, Yoshikawa N; Japanese Study Group of Kidney Disease in Children
  • Journal Title: Clin J Am Soc Nephrol Volume: 9(2) Pages: 271-8
• [Journal Article] Acute kidney injury after acute gastroenteritis in an infant with hereditary hypouricemia (2014)
  • Author(s): Kamei K, Ogura M, Ishimori S, Kaito H, Iijima K, Ito S
  • Journal Title: Eur JPediatr Volume: 173(2) Pages: 247-913
• [Journal Article] Diffuse glomerular nodular lesions in diabetic pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha, an inheritant diabetic gene in humans (2014)
  • Author(s): Hara S, Umeyama K, Yokoo T, Nagashima H, Nagata M
  • Journal Title: PLoS One Volume: 9(3) Pages: e92219
• [Journal Article] Molecular background of urate transporter genes in patients with exercise-induced acute kidney injury (2013)
  • Author(s): Kaito H, Ishimori S, Nozu K, Shima Y, Nakanishi K, Yoshikawa N, Iijima K
  • Journal Title: Am J Nephrol Volume: 38(4) Pages: 316-20
• [Journal Article] SLC26A3 gene analysis in patients with Bartter and Gitelman syndromes and the clinical characteristics of patients with unidentified mutations (2013)
  • Author(s): Ishimori S, Kaito H, Matsunoshita N, Otsubo H, Hashimoto F, Ninchoji T, Nozu K, Morisada N, Iijima K
  • Journal Title: Kobe J Med Sci. Volume: 59(2) Pages: E36-43
• [Journal Article] Different phenotypes of HNF1ß deletion mutants in familial multicystic dysplastic kidneys (2013)
  • Author(s): Hasui M, Kaneko K, Tsuji S, Isozaki Y, Kimata T, Nozu Y, Nozu K, Iijima K
  • Journal Title: Clin Nephrol Volume: 79(6)(PubMed PMID : 23725647) Pages: 484-7
• [Journal Article] First Japanese case of Pierson syndrome with mutations in LAMB2 (2013)
  • Author(s): Togawa H, Nakanishi K, Mukaiyama H, Hama T, Shima Y, Nakano M, Fujita N, Iijima K, Yoshikawa N
  • Journal Title: Pediatr Int. Volume: 55(2) Pages: 229-31
• [Journal Article] Reference ranges for serum cystatin C measurements in Japanese children by using 4 automated assays (2013)
  • Author(s): Yata N, Uemura O, Honda M, Matsuyama T, Ishikura K, Hataya H, Nagai T, Ikezumi Y, Fujita N, Ito S, Iijima K, Saito M, Keneko T, Kitagawa T
  • Journal Title: Clin Exp Nephrol Volume: 17(6) Pages: 872-6
• [Journal Article] Two-year outcome of the ISKDC regimen and frequent-relapsing risk in children with idiopathic nephrotic syndrome (2013)
  • Author(s): Nakanishi K, Iijima K, Ishikura K, Hataya H, Nakazato H, Sasaki S, Honda M, Yoshikawa N; Japanese Study Group of Renal Disease in Children
  • Journal Title: Clin J Am Soc Nephrol Volume: 8(5) Pages: 756-62
• [Journal Article] Endoplasmic reticulum stress with low-dose cyclosporine in frequently relapsing nephrotic syndrome (2013)
  • Author(s): Hama T, Nakanishi K, Mukaiyama H, Shima Y, Togawa H, Sako M, Nozu K, Iijima K, Yoshikawa N
  • Journal Title: Pediatr Nephrol Volume: 28(6) Pages: 903-9
• [Journal Article] Prospective 5-year follow-up of cyclosporine treatment in children with steroid-resistant nephrosis (2013)
  • Author(s): Hamasaki Y, Yoshikawa N, Nakazato H, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Ishikura K, Ito S, Kaneko T, Honda M; for Japanese Study Group of Renal Disease in Children
  • Journal Title: Pediatr Nephrol Volume: 28(5) Pages: 765-71
• [Journal Article] Survey of rituximab treatment for childhood-onset refractory nephrotic syndrome (2013)
  • Author(s): Ito S, Kamei K, Ogura M, Udagawa T, Fujinaga S, Saito M, Sako M, Iijima K
  • Journal Title: Pediatr Nephrol Volume: 28(2) Pages: 257-64
• [Journal Article] Spontaneous remission in children with IgA nephropathy (2013)
  • Author(s): Shima Y, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Sako M, Kaito H, Nozu K, Tanaka R, Iijima K, Yoshikawa N
  • Journal Title: Pediatr Nephrol Volume: 28(1) Pages: 71-6
• [Journal Article] Establishment of a normal reference value for serumβ2 microglobulin in Japanese children : reevaluation of its clinical usefulness (2013)
  • Author(s): Ikezumi Y, Honda M, Matsuyama T, Ishikura K, Hataya H, Yata N, Nagai T, Fujita N, Ito S, Iijima K, Kaneko T, Uemura O
  • Journal Title: Clin Exp Nephrol Volume: 17(1) Pages: 99-105
• [Journal Article] Aberrant Notch1-dependent effects on glomerular parietal epithelial cells promotes collapsing focal segmental glomerulosclerosis with progressive podocyte loss (2013)
  • Author(s): Ueno T, Kobayashi N, Nakayama M, Takashima Y, Uesugi N, Pastan D, Pippin J, Shankland S, Matsusaka Nagata M
  • Journal Title: Kidney Int Volume: 83(6) Pages: 1065-75
• [Journal Article] A Novel Case of Nephrotic Syndrome Caused by Immune-Mediated Acquired LCAT Deficiency (2013)
  • Author(s): Takahashi S, Hiromura K, Tsukida M, Ohishi Y, Hamatani H, Sakurai N, Sakairi T, Ikeuchi H, Kaneko Y, Maeshima A, Kuroiwa T, Yokoo H, Nagata M, Nojima Y
  • Journal Title: J Am Soc Nephrol Volume: 24(8) Pages: 1305-12
• [Journal Article] Henoch-Schönlein purpura nephritis in a patient with IgG4-related disease : a possible association (2013)
  • Author(s): Ito K, Yamada K, Mizushima I, Aizu M, Fujii H, Mizutomi K, Matsumura M, Hayashi K, Yamagishi M, Umehara H, Yamaguchi Y, Nagata M, Kawano M
  • Journal Title: Clin Nephrol Volume: 79(3) Pages: 246-52
• [Journal Article] The direction and role of phenotypic transition between podocytes and parietal epithelial cells in focal segmental glomerulosclerosis (2013)
  • Author(s): Sakamoto K, Ueno T, Kobayashi N, Hara S, Takashima Y, Pastan I, Matsusaka T, Nagata M
  • Journal Title: Am J Physiol Renal Physiol
• [Journal Article] Two-year follow-up of a prospective clinical trial of cyclosporine for frequently relapsing nephrotic syndrome in children (2012)
  • Author(s): Ishikura K, Yoshikawa N, Nakazato H, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Ito S, Yata N, Ando T, Honda M; Japanese Study Group of Renal Disease in Children
  • Journal Title: Clin J Am Soc Nephrol Volume: 7(10) Pages: 1576-83
• [Journal Article] Is the new Schwartz equation derived from serum creatinine and body length suitable for evaluation of renal function in Japanese children? (2012)
  • Author(s): Uemura O, Honda M, Matsuyama T, Ishikura K, Hataya H, Nagai T, Ikezumi Y, Fujita N, Ito S, Iijima K; Japanese Society for Pediatric Nephrology, the Committee of Measures for Pediatric CKD
  • Journal Title: Eur J Pediatr Volume: 171(9) Pages: 1401-4
• [Journal Article] Focal segmental glomerulosclerosis in patients with complete deletion of one WT1 allele (2012)
  • Author(s): Iijima K, Someya T, Ito S, Nozu K, Nakanishi K, Matsuoka K, Ohashi H, Nagata M, Kamei K, Sasaki S
  • Journal Title: Pediatrics Volume: 129(6) Pages: e1621-5
• [Journal Article] Renal biopsy criterion in children with asymptomatic constant isolated proteinuria (2012)
  • Author(s): Hama T, Nakanishi K, Shima Y, Mukaiyama H, Togawa H, Tanaka R, Hamahira K, Kaito H, Iijima K, Yoshikawa N
  • Journal Title: Nephrol Dial Transplant Volume: 27(8) Pages: 3186-90
• [Journal Article] Validity of the Oxford classification of IgA nephropathy in children (2012)
  • Author(s): Shima Y, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Hashimura Y, Kaito H, Sako M, Iijima K, Yoshikawa N
  • Journal Title: Pediatr Nephrol Volume: 27(5) Pages: 783-92
• [Journal Article] Remission of proteinuria in renal amyloidosis secondary to rheumatoid arthritis (2012)
  • Author(s): Ueno T, Takeda Y, Nagata M
  • Journal Title: Nephrol Dial Transplant Volume: 27(2) Pages: 633-9
• [Journal Article] Histological heterogeneity of glomerular segmental lesions in focal segmental glomerulosclerosis (2012)
  • Author(s): Honda K, Taneda S, Yumura W Nitta K, Oda H, Nagata M
  • Journal Title: Int Urol Nephrol Volume: 44(1) Pages: 183-96
• [Journal Article] Characteristic tubulointerstitial nephritis in IgG4-related disease (2012)
  • Author(s): Yamaguchi Y, Kanetsuna Y, Honda K, Kawano M, Yamanaka N, Nagata M
  • Journal Title: Human Pathol Volume: 43(4) Pages: 536-549
• [Journal Article] Clinical and histological changes associated with corticosteroid therapy in IgG4-related tubulointerstitial nephritis (2012)
  • Author(s): Mizushima I, Yamada K, Fujii H, Inoue D, Umehara H, Yamagishi M, Yamaguchi Y, Nagata M, Matsumura M, Kawano M
  • Journal Title: Mod Rheumatol
• [Journal Article] Molecular analysis of TSC2/PKD1 contiguous gene deletion syndrome (2011)
  • Author(s): Oyazato Y, Iijima K, Emi M, Sekine T, Kamei K, Takanashi J, Nakao H, Namai Y, Nozu K, Matsuo M
  • Journal Title: Kobe J Med Sci. Volume: 57(1) Pages: E1-10
• [Journal Article] Identification of FOXP3-negative regulatory T-like (CD4(+)CD25(+)CD127(low)) cells in patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (2011)
  • Author(s): Otsubo K, Kanegane H, Kamachi Y, Kobayashi I, Tsuge I, Imaizumi M, Sasahara Y, Hayakawa A, Nozu K, Iijima K, Ito S, Horikawa R, Nagai Y, Takatsu K, Mori H, Ochs HD, Miyawaki T
  • Journal Title: Clin Immunol Volume: 141(1) Pages: 111-20
• [Journal Article] A surviving case of papillorenal syndrome with the phenotype of Potter sequence (2011)
  • Author(s): Fujioka K, Morioka I, Nozu K, Nishimoto M, Amano M, Tagami M, Honda S, Yokoyama N, Yamada H, Iijima K, Matsuo M
  • Journal Title: Pediatr Int. Volume: 53(3) Pages: 406-8
• [Journal Article] Maintenance therapy with mycophenolate mofetil after rituximab in pediatric patients with steroid-dependent nephrotic syndrome (2011)
  • Author(s): Ito S, Kamei K, Ogura M, Sato M, Fujimaru T, Ishikawa T, Udagawa T, Iijima K
  • Journal Title: Pediatr Nephrol Volume: 26(10) Pages: 1823-8
• [Journal Article] Recurrent EIARF and PRES with severe renal hypouricemia by compound heterozygous SLC2A9 mutation (2011)
  • Author(s): Shima Y, Nozu K, Nozu Y, Togawa H, Kaito H, Matsuo M, Iijima K, Nakanishi K, Yoshikawa N
  • Journal Title: Pediatrics Volume: 127(6) Pages: e1621-5
• [Journal Article] Age, gender, and body length effects on reference serum creatinine levels determined by an enzymatic method in Japanese children : a multicenter study (2011)
  • Author(s): Uemura O, Honda M, Matsuyama T, Ishikura K, Hataya H, Yata N, Nagai T, Ikezumi Y, Fujita N, Ito S, Iijima K, Kitagawa T
  • Journal Title: Clin Exp Nephrol Volume: 15(5) Pages: 694-9
• [Journal Article] Long-term results of a randomized controlled trial in childhood IgA nephropathy (2011)
  • Author(s): Kamei K, Nakanishi K, Ito S, Saito M, Sako M, Ishikura K, Hataya H, Honda M, Iijima K, Yoshikawa N; Japanese Pediatric IgA Nephropathy Treatment Study Group
  • Journal Title: Clin J Am Soc Nephrol Volume: 6(6) Pages: 1301-7
• [Journal Article] Treatment strategies for Henoch-Schönlein purpura nephritis by histological and clinical severity (2011)
  • Author(s): Ninchoji T, Kaito H, Nozu K, Hashimura Y, Kanda K, Kamioka I, Shima Y, Hamahira K, Nakanishi K, Tanaka R, Yoshikawa N, Iijima K, Matsuo M
  • Journal Title: Pediatr Nephrol Volume: 26(4) Pages: 563-9
• [Journal Article] Focal segmental glomerulosclerosis as a complication of hepatitis B virus infection (2011)
  • Author(s): Sakai K, Morito N, Usui J, Hagiwara M, Hiwatashi A, Fukuda K, Nanmoku T, Toda T, Matsui N, Nagata M, Yamagata K
  • Journal Title: Nephrol Dial Transplant Volume: 26(1) Pages: 371-3
• [Journal Article] Morphological and functional analyses of two infants with obstructive renal dysplasia (2011)
  • Author(s): Miura K, Sekine T, Nishimura R, Kanamori Y, Yanagisawa A, Sakai K, Nagata M, Igarashi T
  • Journal Title: Clin Exp Nephrol Volume: 15(4) Pages: 602-6
• [Journal Article] A case of multicentric Castleman's disease with membranoproliferative glomerulonephritis type 3-like lesion (2011)
  • Author(s): Nagai K, Usui J, Noguchi K, Unai K, Hiwatashi A, Arakawa Y, Togashi A, Morito N, Saito C, Yoh K, Tsuruoka S, Kojima H, Aita K, Nagata M, Yamagata K
  • Journal Title: Pathol Int. Volume: 61(11) Pages: 686-90
• [Presentation] Heterozygous microdeletion of 16q covering SALL1 and RPGRIP1L could be a novel contiguous gene syndrome with renal impairment (2013)
  • Author(s): Morisada N, Taniguchi-Ikeda M, Ishimori S, Ninchoji T, Kaito H, Nozu K, Adach Mi, Takeshima Y, SekineT, Iijima K
  • Organizer: American Society of Human Genetics
  • Place of Presentation: Boston
  • Year and Date: 20130000
• [Presentation] Natural History and Protein Expression Pattern in Autosomal Recessive Alport Syndrome Based on the Comprehensive Strategy for Genetic Analysis (2013)
  • Author(s): Kaito H, Nozu K, Oka M, Morisada N, Ninchoji T, Nakanishi K, Yoshikawa N, Iijima K
  • Organizer: American Society of Nephrology KIDNEY WEEK
  • Place of Presentation: Atlanta
  • Year and Date: 20130000
• [Presentation] 遺伝性腎疾患の最近の知見 (2013)
  • Author(s): 飯島一誠
  • Organizer: 第48回日本小児腎臓病学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 20130000
• [Presentation] CAKUTの分子遺伝学的アプローチ (2013)
  • Author(s): 飯島一誠
  • Organizer: 第22回日本小児泌尿器科学会総会
  • Place of Presentation: 東京
  • Year and Date: 20130000
• [Presentation] 総排泄腔遺残をともなった1q21.1欠失症候群の1女児例 (2013)
  • Author(s): 森貞直哉,野田俊輔,降?めぐみ,池田真理子,竹島泰弘,飯島一誠
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 仙台
  • Year and Date: 20130000
• [Presentation] Genetical and Clinical Aspects of X-Linked Alport Syndrome in Males with Positive Staining of the alpha5(IV) Chain (2012)
  • Author(s): Hashimura Y, Nozu K, Kaito H, Ohtsubo H, Hashimoto F, Ishimori S, Ninchoji T, Morisada N, Nakanishi K, Yoshikawa N, Iijima K
  • Organizer: 45th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 20121101-04
• [Book] 腎低形成・異形成.小児腎臓病学,日本小児腎臓病学会編(編集主幹飯島一誠他) (2012)
  • Author(s): 長田道夫
  • Total Pages: 39-42
  • Publisher: 診断と治療社