Isolated proteinuria due to CUBN homozygous mutation – challenging the investigative paradigm
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 sup...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12882-019-1474-z |
| _version_ | 1828308447461900288 |
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| author | Kushani Jayasinghe Susan M. White Peter G. Kerr Duncan MacGregor Zornitza Stark Ella Wilkins Cas Simons Andrew Mallett Catherine Quinlan |
| author_facet | Kushani Jayasinghe Susan M. White Peter G. Kerr Duncan MacGregor Zornitza Stark Ella Wilkins Cas Simons Andrew Mallett Catherine Quinlan |
| author_sort | Kushani Jayasinghe |
| collection | DOAJ |
| description | 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). Conclusions 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. |
| first_indexed | 2024-04-13T15:13:32Z |
| format | Article |
| id | doaj.art-8c593240981a4e889cdf6eabad843a6b |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-04-13T15:13:32Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-8c593240981a4e889cdf6eabad843a6b2022-12-22T02:41:57ZengBMCBMC Nephrology1471-23692019-08-012011510.1186/s12882-019-1474-zIsolated proteinuria due to CUBN homozygous mutation – challenging the investigative paradigmKushani Jayasinghe0Susan M. White1Peter G. Kerr2Duncan MacGregor3Zornitza Stark4Ella Wilkins5Cas Simons6Andrew Mallett7Catherine Quinlan8Department of Nephrology, Monash Medical CentreThe KidGen Collaborative, Australian Genomics Health AllianceDepartment of Nephrology, Monash Medical CentreDepartment of Pathology, Royal Children’s HospitalMurdoch Children’s Research InstituteMurdoch Children’s Research InstituteMurdoch Children’s Research InstituteMurdoch Children’s Research InstituteMurdoch Children’s Research InstituteAbstract 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). Conclusions 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.http://link.springer.com/article/10.1186/s12882-019-1474-zGenomicsGeneticsChronic kidney disease |
| spellingShingle | Kushani Jayasinghe Susan M. White Peter G. Kerr Duncan MacGregor Zornitza Stark Ella Wilkins Cas Simons Andrew Mallett Catherine Quinlan Isolated proteinuria due to CUBN homozygous mutation – challenging the investigative paradigm BMC Nephrology Genomics Genetics Chronic kidney disease |
| title | Isolated proteinuria due to CUBN homozygous mutation – challenging the investigative paradigm |
| title_full | Isolated proteinuria due to CUBN homozygous mutation – challenging the investigative paradigm |
| title_fullStr | Isolated proteinuria due to CUBN homozygous mutation – challenging the investigative paradigm |
| title_full_unstemmed | Isolated proteinuria due to CUBN homozygous mutation – challenging the investigative paradigm |
| title_short | Isolated proteinuria due to CUBN homozygous mutation – challenging the investigative paradigm |
| title_sort | isolated proteinuria due to cubn homozygous mutation challenging the investigative paradigm |
| topic | Genomics Genetics Chronic kidney disease |
| url | http://link.springer.com/article/10.1186/s12882-019-1474-z |
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