title: Association of PAX2 and Other Gene Mutations with the Clinical Manifestations of Renal Coloboma Syndrome.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Disease Control, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Department of Disease Control, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.|Division of Blood Purification, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Furuichi
authors.affiliation: Departments of Ophthalmology and Visual Science, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Higashide
authors.affiliation: Departments of Ophthalmology and Visual Science, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sakurai
authors.affiliation: Division of Nephrology, Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Division of Nephrology, Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shinozaki
authors.affiliation: Department of Disease Control, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hara
authors.affiliation: Division of Nephrology, Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Department of Disease Control, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.|Division of Blood Purification, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Sakai
authors.affiliation: Departments of Ophthalmology and Visual Science, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Department of Disease Control, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Division of Nephrology, Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada
mesh_terms: D000595:Amino Acid Sequence; D003103:Coloboma / Q000235:genetics* / Q000473:pathology*; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009900:Optic Nerve / Q000002:abnormalities; D051762:PAX2 Transcription Factor / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D051437:Renal Insufficiency / Q000235:genetics* / Q000473:pathology*; D014718:Vesico-Ureteral Reflux / Q000235:genetics* / Q000473:pathology*
chemical_list: D051762:PAX2 Transcription Factor