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Title: | Isolated proteinuria due to CUBN homozygous mutation - Challenging the investigative paradigm. | Authors: | MacGregor D.;Stark Z.;Wilkins E.;Simons C.;Mallett A.;Quinlan C.;Jayasinghe K.;White S.M.;Kerr P.G. | Institution: | (Jayasinghe, Kerr) Department of Nephrology, Monash Medical Centre, Melbourne, Australia (Jayasinghe, Kerr) Monash University, Melbourne, Australia (Jayasinghe, Stark, Wilkins, Simons, Mallett, Quinlan) Murdoch Children's Research Institute, Melbourne, Australia (Jayasinghe, White, Stark, Wilkins, Simons, Mallett, Quinlan) KidGen Collaborative, Australian Genomics Health Alliance, VIC, Australia (White, Stark) Department of Paediatrics, University of Melbourne, VIC, Australia (White, Stark, Wilkins) Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia (MacGregor) Department of Pathology, Royal Children's Hospital, Melbourne, Australia (Mallett) Kidney Health Service and Conjoint Renal Research Laboratory, Royal Brisbane and Women's Hospital, Brisbane, Australia (Mallett) Institute for Molecular Bioscience, Faculty of Medicine, University of Queensland, Brisbane, Australia (Quinlan) Department of Paediatric Nephrology, Royal Children's Hospital, 50 Flemington Street, Parkville, Australia | Issue Date: | 5-Sep-2019 | Copyright year: | 2019 | Publisher: | BioMed Central Ltd. (E-mail: info@biomedcentral.com) | Place of publication: | United Kingdom | Publication information: | BMC Nephrology. 20 (1) (no pagination), 2019. Article Number: 330. Date of Publication: 22 Aug 2019. | Journal: | BMC Nephrology | Abstract: | Background: Proteinuria is a common clinical presentation, the diagnostic workup for which involves many non-invasive and invasive investigations. We report on two siblings that highlight the clinically relevant functional role of cubulin for albumin resorption in the proximal tubule and supports the use of genomic sequencing early in the diagnostic work up of patients who present with proteinuria. Case presentation: An 8-year-old boy was referred with an incidental finding of proteinuria. All preliminary investigations were unremarkable. Further assessment revealed consanguineous family history and a brother with isolated proteinuria. Renal biopsy demonstrated normal light microscopy and global glomerular basement membrane thinning 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 and their further research genomic analysis implicated a homozygous stop-gain variant in CUBN (10p12.31). Conclusion(s): 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 ability of genomic testing to identify genetic causes of nephropathy within expanding associated phenotypic spectra. Genomic sequencing, undertaken earlier in the diagnostic trajectory, may reduce the need for invasive investigations and the time to definitive diagnosis for patients and families.Copyright © 2019 The Author(s). | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1186/s12882-019-1474-z | PubMed URL: | 31438875 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31438875] | ISSN: | 1471-2369 (electronic) | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/35945 | Type: | Article | Subjects: | single nucleotide polymorphism whole genome sequencing aldosterone antagonist/dt [Drug Therapy] angiotensin antagonist/dt [Drug Therapy] renin inhibitor/dt [Drug Therapy] *CUBN gene treatment response abdominal pain article case report child clinical article family history gene *gene mutation *homozygosity human incidental finding male microalbuminuria/di [Diagnosis] microarray analysis mutational analysis pathogenesis protein electrophoresis *proteinuria/di [Diagnosis] *proteinuria/dt [Drug Therapy] *proteinuria/et [Etiology] school child incidental finding male microalbuminuria / diagnosis microarray analysis mutational analysis pathogenesis protein electrophoresis *proteinuria / *diagnosis / *drug therapy / *etiology school child case report treatment response whole genome sequencing Article abdominal pain single nucleotide polymorphism child clinical article family history gene *gene mutation *homozygosity human |
Type of Clinical Study or Trial: | Case series or case report |
Appears in Collections: | Articles |
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