Association of PAX2 and Other Gene Mutations with the Clinical Manifestations of Renal Coloboma Syndrome

PLoS One. 2015 Nov 16;10(11):e0142843. doi: 10.1371/journal.pone.0142843. eCollection 2015.


Background: Renal coloboma syndrome (RCS) is characterized by renal anomalies and optic nerve colobomas. PAX2 mutations contribute to RCS. However, approximately half of the patients with RCS have no mutation in PAX2 gene.

Methods: To investigate the incidence and effects of mutations of PAX2 and 25 candidate genes, patient genes were screened using next-generation sequence analysis, and candidate mutations were confirmed using Sanger sequencing. The correlation between mutations and clinical manifestation was evaluated.

Result: Thirty patients, including 26 patients (two families of five and two, 19 sporadic cases) with RCS, and 4 optic nerve coloboma only control cases were evaluated in the present study. Six PAX2 mutations in 21 probands [28%; two in family cohorts (n = 5 and n = 2) and in 4 out of 19 patients with sporadic disease] including four novel mutations were confirmed using Sanger sequencing. Moreover, four other sequence variants (CHD7, SALL4, KIF26B, and SIX4) were also confirmed, including a potentially pathogenic novel KIF26B mutation. Kidney function and proteinuria were more severe in patients with PAX2 mutations than in those without the mutation. Moreover, the coloboma score was significantly higher in patients with PAX2 gene mutations. Three out of five patients with PAX2 mutations had focal segmental glomerulosclerosis (FSGS) diagnosed from kidney biopsies.

Conclusion: The results of this study identify several new mutations of PAX2, and sequence variants in four additional genes, including a novel potentially pathogenic mutation in KIF26B, which may play a role in the pathogenesis of RCS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Coloboma / genetics*
  • Coloboma / pathology*
  • Exons / genetics
  • Family
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Kidney / pathology
  • Male
  • Molecular Sequence Data
  • Mutation / genetics*
  • Optic Nerve / abnormalities
  • PAX2 Transcription Factor / chemistry
  • PAX2 Transcription Factor / genetics*
  • Pedigree
  • Renal Insufficiency / genetics*
  • Renal Insufficiency / pathology*
  • Vesico-Ureteral Reflux / genetics*
  • Vesico-Ureteral Reflux / pathology*


  • PAX2 Transcription Factor

Supplementary concepts

  • Coloboma of optic nerve
  • Papillorenal syndrome

Grants and funding

This work was supported in part by Grants-in-Aids from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese Government (#22590883, #26293126, #15K15328). There was no additional external funding received for this study.