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Kidney Week

Abstract: TH-PO541

Biallelic CUBN Variants as a Cause of Isolated Proteinuria - Challenging the Investigative Paradigm

Session Information

  • Trainee Case Reports - I
    October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Reports

  • 1002 Genetic Diseases of the Kidney: Non-Cystic


  • Jayasinghe, Kushani C., Monash Health, Clayton, New South Wales, Australia
  • Quinlan, Catherine, The Royal Children's Hospital, Melbourne, Victoria, Australia
  • Wilkins, Ella J., Victorian Clinical Genetics Services, Parkville, New South Wales, Australia
  • White, Susan M., Victorian Clinical Genetics Services, Parkville, New South Wales, Australia
  • Simons, Cas, Murdoch Childrens Research Institute, Parkville, New South Wales, Australia
  • Mallett, Andrew John, Royal Brisbane and Women's Hospital, Stafford, Queensland, Australia

Proteinuria is a common kidney presentation. Historically, diagnostic workup of patients with isolated proteinuria involved thorough urinalysis, imaging and blood sampling before potentially proceeding to renal biopsy. However recent advances have resulted in reduced cost and increased availability of genomic sequencing for establishing clinical diagnoses.

Case Description

An 8year old boy was referred with an incidental finding of persistent proteinuria during investigation for nonspecific abdominal pain. He had no haematuria and had normal serum albumin. All other investigations including blood analysis for haematological, biochemical and immunological parameters, renal ultrasound, ophthalmology and audiology assessment were unremarkable. Further assessment revealed consanguineous family history and a brother also with isolated proteinuria. Renal biopsy demonstrated normal light microscopy and global uniform thinning of the glomerular basement membrane on electron microscopy. Chromosomal microarray revealed long continuous stretches of homozygosity (LCSH) representing ~4.5% of the genome. Shared regions of LCSH between the brothers were identified using the Genomic Oligoarray and single nucleotide polymorphism (SNP) Evaluation tool. Examination of these regions implicated CUBN, on chromosome 10p12.31. Research whole genome sequencing of both affected individuals was performed with informed consent (HREC/15/QRCH/126). This revealed a homozygous stop-gain variant in CUBN (NM_001081.3, c.4689_4690delTAinsAT, p.(CysIle1263*), ACMG Class 5).


CUBN mutations have been implicated as a hereditary cause of megaloblastic anaemia and variable proteinuria. This is the second reported family with isolated proteinuria due to biallelic CUBN variants in the absence of megaloblastic anaemia, demonstrating the utility of genomics to identify single gene causes of nephropathy, and in doing so, to expand the associated phenotypic spectrum. Therefore, genomic sequencing, undertaken earlier in the diagnostic workup, has the potential to reduce the need for invasive investigations and to reduce the time to definitive diagnosis for patients and families.