A novel truncating PAX2 mutation in a boy with renal coloboma syndrome with focal segmental glomerulosclerosis causing rapid progression to end-stage kidney disease
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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.
KeywordsPAX2 Renal coloboma syndrome Focal segmental glomerulosclerosis Truncating mutation
Focal segmental glomerulosclerosis
Renal coloboma syndrome
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.
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.
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