Detection of a splice site variant in a patient with glomerulopathy and fibronectin deposits

Yurika Tsuji, Kandai Nozu, Tadashi Sofue, Shigeo Hara, Keita Nakanishi, Tomohiko Yamamura, Shogo Minamikawa, Yoshimi Nozu, Hiroshi Kaito, Junya Fujimura, Tomoko Horinouchi, Naoya Morisada, Ichiro Morioka, Mariko Taniguchi-Ikeda, Masafumi Matsuo, Kazumoto Iijima

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Background/Aims: Glomerulopathy with fibronectin deposits (GFND; OMIM: 601894) is a very rare inherited kidney disease caused by pathogenic variants in the FN1 gene. Only 9 exonic pathogenic variants in FN1, 9 at the heparin-binding site, and 1 at the integrin-binding site have been reported. No intronic variants in FN1 have been detected. Methods: We found a pathogenic intronic variant in intron 36 (c.5888-2A>G) located at the heparin-binding site. To determine whether this mutation influences splicing processes, we conducted RT-PCR analysis and an in vitro splicing assay using minigene construction. Results: RT-PCR using RNA extracted from leukocytes of the proband failed because of the low expression of FN1 mRNA in leukocytes. We conducted in vitro functional splicing analysis using minigenes and found that c.5888-2A>G caused a 12 bp deletion at exon 37 by the activation of a novel splicing acceptor site within exon 37. We were able to detect the same abnormal transcript in mRNA extracted from the patient's urinary sediment and confirmed the pathogenicity of c.5888-2A>G by both RT-PCR using the patient sample and an in vitro splicing assay. Conclusion: Intronic variants can cause GFND. Minigene analysis is useful for determining the pathogenicity of the intronic variants and could be used for all inherited kidney diseases.

Original languageEnglish
Pages (from-to)166-171
Number of pages6
Issue number2
Publication statusPublished - 02-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nephrology
  • Physiology (medical)
  • Urology


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