Molecular analysis for inherited tubulopathies

2008 Fiscal Year Final Research Report

• Project/Area Number: 19790720
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Kobe University
• Principal Investigator: NOZU Kandai Kobe University, 医学部・附属病院, 助教 (70362796)
• Project Period (FY): 2007 – 2008
• Keywords: Bartter症候群 / Gitelman症候群 / 尿中落下細胞 / チャネル・トランスポーター

Research Abstract

Bartter症候群(BS)、Gitelman症候群(GS)は常染色体劣性尿細管機能異常症で、低カリウム血症、代謝性アルカローシス、高レニン、高アルドステロン血症などを特徴とする。日本人におけるこれらの疾患を有する患者において、臨床的および遺伝学的検討はこれまで行われてこなかったが、私たちは今回の研究で、現在までに53例で遺伝子解析による確定診断を行ってきた。その結果、典型例ではそのほとんどで遺伝子変異を同定することができ、本疾患においては遺伝子診断率が高い疾患であることが分かった。また、解析方法に関する工夫を行い、尿中落下細胞からmRNAを抽出し、RT-PCRを用いて解析を行うという非侵襲的かつ斬新な方法を導入することで、遺伝子診断率を向上させることに成功し、さらに、これまでこれらの疾患で遺伝子診断率が低かった原因として、従来の直接シークエンス法による解析では広範囲のヘテロ接合体欠失の検出はできず、BS患者においてはこの変異が多いためであることを明らかにした。そこで、PCR半定量法を導入することで、それらの変異の検出に成功した。現在まで私たちは90%以上の患者において遺伝子変異の検出に成功した。

Research Products

• [Journal Article] Detection by multiplex ligation-dependent probe amplification of large deletion mutations in the COL4A5 gene in female patients with Alport syndrome (2009)
  • Author(s): Nozu K, Krol RP, Nakanishi K, Yoshikawa N, Nozu Y, Ohtsuka Y, Iijima K, Matsuo M.
  • Journal Title: Pediatr Nephrol (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Molecular analysis of digenic inheritance in Bartter syndrome with sensorineural deafness (2008)
  • Author(s): Nozu K, Inagaki T, Fu XJ, Nozu Y, Kaito H, Kanda K, Sekine T, Igarashi T, Nakanishi K, Yoshikawa N, Iijima K, Matsuo M
  • Journal Title: J Med Genet 45 Pages: 182-186
  • Peer Reviewed
• [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: 2525-2530
  • Peer Reviewed
• [Journal Article] Diverse splicing abnormality caused by a homozygous mutation in the thiazide-sensitive sodiumchloride cotransporter gene in a patient with Gitelman's syndrome (2008)
  • Author(s): Iida K, Nozu K, Takahashi Y, Okimura Y, Kaji H, Matsuo M, Chihara K.
  • Journal Title: Am J Kidney Dis 51 Pages: 1077-1078
  • Peer Reviewed
• [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 Pages: 2085-2090
  • Peer Reviewed
• [Journal Article] Oxidative imbalance in idiopathic renal hypouricemia (2008)
  • Author(s): Kaneko K, Taniguchi N, Tanabe Y, Nakano T, Hasui M, Nozu K.
  • Journal Title: Pediatr Nephrol (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Atypical phenotype of type I Bartter syndrome accompanied by focal segmental glomerulosclerosis (2008)
  • Author(s): Yamazaki H, Nozu K, Narita I, Nagata M, Nozu Y, Fu XJ, Matsuo M, Iijima K, Gejyo F.
  • Journal Title: Pediatr Nephrol (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Detection of a transcript abnormality in mRNA of the SLC12A3 gene extracted from urinary sediment cells of a patient with Gitelman's syndrome (2007)
  • Author(s): Kaito H, Nozu K, Fu XJ, Kamioka I, Fujita T, Kanda K, Krol RP, Suminaga R, Ishida A, Iijima K, Matsuo M
  • Journal Title: Pediatric Research 61(4) Pages: 502-505
  • Peer Reviewed
• [Journal Article] OCRL1 mutations in patients with Dent phenotype in Japan. Pediatr Nephrol (2007)
  • Author(s): Sekine T, Nozu K, Iyengar R, Fu XJ, Matsuo M, Tanaka R, Iijima K, Matsui M, Harita Y, Inatomi J, Igarashi T
  • Journal Title: 22 Pages: 975-980
  • Peer Reviewed
• [Journal Article] A novel mutation in KCNJ1 in a Bartter syndrome case diagnosed as pseudohypoaldosteronism (2007)
  • Author(s): Nozu K, Fu XJ, Kaito H, Kanda K, Yokoyama N, Krol PR, Nakajima T, Kajiyama M, Iijima K, Matsuo M
  • Journal Title: Pediatr Nephrol 22 Pages: 1219-1223
  • Peer Reviewed
• [Journal Article] Molecular Analysis of Patients With Type III Bartter Syndrome : Picking Up Large Heterozygous Deletions With Semiquantitative PCR (2007)
  • Author(s): Nozu K, Fu XJ, Nakanishi K, Yoshikawa N, Kaito H, Kanda K, Krol RP, Miyashita R, Kamitsuji H, Kanda S, Hayashi Y, Satomura K, Shimizu N, Iijima K, Matsuo M.
  • Journal Title: Pediatr Res 62 Pages: 364-369
  • Peer Reviewed
• [Presentation] Bartter症候群とGitelman症候群の病型と臨床症状 (2008)
  • Author(s): 野津寛大
  • Organizer: 第43回日本小児腎臓病学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20080613-14