A novel truncating PAX2 mutation in a boy with renal coloboma syndrome with focal segmental glomerulosclerosis causing rapid progression to end-stage kidney disease

  • Ken Saida
  • Koichi Kamei
  • Naoya Morisada
  • Masao Ogura
  • Kentaro Ogata
  • Kentaro Matsuoka
  • Kandai Nozu
  • Kazumoto Iijima
  • Shuichi ItoEmail author
Case Report


Renal coloboma syndrome (RCS, MIM#120330), also known as papillorenal syndrome, is an inherited autosomal dominant disease characterized by ocular and/or renal involvement due to PAX2 mutation. The renal involvement typically consists of a hypo/dysplatic kidney and/or vesicoureteral reflux. Recent studies reported that missense PAX2 mutations cause familial focal segmental glomerular sclerosis (FSGS) without renal morphological malformations. To date, the reports of genotype–phenotype correlation including pathological findings regarding PAX2 mutations are scarce. We report a case of RCS with a novel PAX2 mutation that was pathologically diagnosed as FSGS and rapidly progressed to end-stage kidney failure (ESKD) with a review of past literature. A 6-year-old boy, who had bilateral coloboma and loss of vision in the left eye, was noted non-nephrotic proteinuria and renal dysfunction via school urine screening. Abdominal ultrasound showed no renal and urinary tract malformations and kidney biopsy showed FSGS. Genetic analysis revealed a novel insertion-deletion mutation in PAX2 (NM003987.4: c.70_72delinsA; p.Gly24Argfs*29). His kidney function deteriorated gradually during the following 2 years and kidney transplantation was performed at 9 years of age. In previous reports describing PAX2 mutations with FSGS, affected individuals with missense PAX2 mutations developed ESKD in adulthood, whereas one case with truncating PAX2 mutations developed ESKD in childhood similar to the current case. Our case highlighted the association of truncating PAX2 mutations with the risk of rapid progression to ESKD. Thus, PAX2 mutations should be included in genetic screening for such cases even in the absence of renal and urinary tract malformations.


PAX2 Renal coloboma syndrome Focal segmental glomerulosclerosis Truncating mutation 



Focal segmental glomerulosclerosis


Renal coloboma syndrome


Vesicoureteral reflux



The authors would like to thank Dr. Akira Saitoh at St. Marianna University School of Medicine for patient’s clinical follow-up and Dr. Koichi Nakanishi at University of the Ryukyu for performing the genetic tests for WT1 and NPHS2 mutations.

Compliance with ethical standards

Conflict of interest

None of the authors have any conflicts of interest to declare.

Ethical approval

This study was approved by the ethics committee of the National Center for Child Health and Development in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Consent for publication

A consent for publication was obtained from the parent.


  1. 1.
    Bower MA, Schimmenti LA, Eccles MR. Renal coloboma syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Smith RJH et al. editors. GeneReviews®. Seattle: University of Washington; 1993.Google Scholar
  2. 2.
    Bower M, Salomon R, Allanson J, Antignac C, Benedicenti F, Benetti E, et al. Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database. Hum Mutat. 2012;33(3):457–66. Scholar
  3. 3.
    Okumura T, Furuichi K, Higashide T, Sakurai M, Hashimoto S, Shinozaki Y, et al. Association of PAX2 and Other Gene Mutations with the Clinical Manifestations of Renal Coloboma Syndrome. PLoS ONE. 2015;10(11):e0142843. Scholar
  4. 4.
    Weaver RG, Cashwell LF, Lorentz W, Whiteman D, Geisinger KR, Ball M. Optic nerve coloboma associated with renal disease. Am J Med Genet. 1988;29(3):597–605. Scholar
  5. 5.
    Schimmenti LA, Cunliffe HE, McNoe LA, Ward TA, French MC, Shim HH, et al. Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations. Am J Hum Genet. 1997;60(4):869–78.Google Scholar
  6. 6.
    Laimutis K, Jackson C, Xu X, Warman B, Sarunas R, Andriuskeviciute I, et al. Typical renal-coloboma syndrome phenotype in a patient with a submicroscopic deletion of the PAX2 gene. American journal of medical genetics Part A. 2012;158A(6):1437–41. Scholar
  7. 7.
    Bower MA, Schimmenti LA, Eccles MR PAX2-related disorder In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K editors. GeneReviews®. Seattle: University of Washington; 1993.Google Scholar
  8. 8.
    Barua M, Stellacci E, Stella L, Weins A, Genovese G, Muto V, et al. Mutations in PAX2 associate with adult-onset FSGS. J Am Soc Nephrol. 2014;25(9):1942–53. Scholar
  9. 9.
    Vivante A, Chacham OS, Shril S, Schreiber R, Mane SM, Pode-Shakked B, et al. Dominant PAX2 mutations may cause steroid-resistant nephrotic syndrome and FSGS in children. Pediatr Nephrol. 2019. Scholar
  10. 10.
    Schimmenti LA. Renal coloboma syndrome. Eur J Human Genetics EJHG. 2011;19(12):1207–12. Scholar

Copyright information

© Japanese Society of Nephrology 2019

Authors and Affiliations

  1. 1.Division of Nephrology and RheumatologyNational Center for Child Health and DevelopmentTokyoJapan
  2. 2.Department of PediatricsKobe University Graduate School of MedicineKobeJapan
  3. 3.Department of Clinical GeneticsHyogo Prefectural Kobe Children’s HospitalKobeJapan
  4. 4.Department of PathologyFederation of National Service Personnel Mutual Aid Associations Tachikawa HospitalTachikawa-shiJapan
  5. 5.Division of PathologyDokkyo Medical University Koshigaya HospitalKoshigayaJapan
  6. 6.Department of PediatricsYokohama City UniversityYokohamaJapan

Personalised recommendations