Identification of mutations in FN1 leading to glomerulopathy with fibronectin deposits

Hiromi Ohtsubo, Taro Okada, Kandai Nozu, Yutaka Takaoka, Akemi Shono, Katsuhiko Asanuma, Lifang Zhang, Koichi Nakanishi, Mariko Taniguchi-Ikeda, Hiroshi Kaito, Kazumoto Iijima, Shun ichi Nakamura

研究成果: ジャーナルへの寄稿学術論文査読

37 被引用数 (Scopus)

抄録

Background: Glomerulopathy with fibronectin deposits (GFND) is a rare autosomal dominant disease characterized by massive fibronectin deposits, leading to end-stage renal failure. Although mutations within the heparin-binding domains of the fibronectin 1 gene (FN1) have been associated with GFND, no mutations have been reported within the integrin-binding domains. Methods: In this study, FN1 mutational analysis was conducted in 12 families with GFND. Biochemical and functional features of mutated proteins were examined using recombinant fibronectin fragments encompassing both the integrin- and heparin-binding domains. Results: We report six FN1 mutations from 12 families with GFND, including five that are novel (p.Pro969Leu, p.Pro1472del, p.Trp1925Cys, p.Lys1953_Ile1961del, and p.Leu1974Pro). p.Pro1472del is localized in the integrin-binding domain of fibronectin, while the others are in heparin-binding domains. We detected p.Tyr973Cys, p.Pro1472del, and p.Leu1974Pro mutations in multiple families, and haplotype analysis implied that p.Pro1472del and p.Leu1974Pro are founder mutations. The protein encoded by the novel integrin-binding domain mutation p.Pro1472del showed decreased cell binding ability via the integrin-binding site. Most affected patients developed urine abnormalities during the first or second decade of life, and some mutation carriers were completely asymptomatic. Conclusions: This is the second large-scale analysis of GFND families and the first report of an integrin-binding domain mutation. These findings may help determine the pathogenesis of GFND.

本文言語英語
ページ(範囲)1459-1467
ページ数9
ジャーナルPediatric Nephrology
31
9
DOI
出版ステータス出版済み - 01-09-2016
外部発表はい

All Science Journal Classification (ASJC) codes

  • 小児科学、周産期医学および子どもの健康
  • 腎臓病学

フィンガープリント

「Identification of mutations in FN1 leading to glomerulopathy with fibronectin deposits」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル