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It is characterized by progressive and non-specific glomerulosclerosis with irregular thickening of the glomerular basement membrane (GBM). At times, the histopathologic picture is dominated by lesions that are consistent with focal and segmental glomerulosclerosis or IgA nephropathy. Here, we report the cases of two related individuals (mother and son) who were diagnosed with\n                    <jats:italic>COL4A5<\/jats:italic>\n                    -related Alport syndrome due to a missense variant (p.Gly1170Ser) in a G-X-Y repeat and found to present the same highly unusual histopathological abnormalities on their kidney biopsies. One of the abnormalities shared, which does not appear to have been reported, was reduced COL4A5 immunolabeling that was limited to Bowman\u2019s capsule even though the ultrastructure of the GBM was distorted. The other abnormality was superimposed segmental IgA deposition in both individuals, accompanied by mesangial changes in the mother. We feel that these findings provide novel insight into the mechanisms of disease manifestation in Alport syndrome. They suggest, in particular, that collagen expression and\/or assemblies in Bowman\u2019s capsule is more vulnerable to missense mutations in\n                    <jats:italic>COL4A5<\/jats:italic>\n                    than elsewhere in the kidney. Our findings also suggest that certain coinherited gene polymorphisms act as unexpectedly important phenotypic determinants in\n                    <jats:italic>COL4A<\/jats:italic>\n                    -related disorders.\n                  <\/jats:p>","DOI":"10.1007\/s40620-024-01942-7","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T02:01:52Z","timestamp":1714096912000},"page":"769-772","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["X-linked Alport syndrome presenting in mother and son with the same unique histopathological features"],"prefix":"10.1093","volume":"37","author":[{"given":"Nicolas A. D.","family":"Bergeron","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre P.","family":"Garneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Rousseau-Gagnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Riopel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5569-6258","authenticated-orcid":false,"given":"Paul","family":"Isenring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"1942_CR1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022296","author":"BG Hudson","year":"2003","unstructured":"Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG (2003) Alport\u2019s syndrome, Goodpasture\u2019s syndrome, and type IV collagen. N Engl J Med. https:\/\/doi.org\/10.1056\/NEJMra022296","journal-title":"N Engl J Med"},{"issue":"2","key":"1942_CR2","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1007\/s10157-018-1629-4","volume":"23","author":"K Nozu","year":"2019","unstructured":"Nozu K, Nakanishi K, Abe Y et al (2019) A review of clinical characteristics and genetic backgrounds in Alport syndrome. Clin Exp Nephrol 23(2):158\u2013168. https:\/\/doi.org\/10.1007\/s10157-018-1629-4","journal-title":"Clin Exp Nephrol"},{"key":"1942_CR3","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2021.04.017","author":"J Savige","year":"2021","unstructured":"Savige J, Harraka P (2021) Pathogenic variants in the genes affected in Alport syndrome (COL4A3-COL4A5) and their association with other kidney conditions: a review. Am J Kidney Dis. https:\/\/doi.org\/10.1053\/j.ajkd.2021.04.017","journal-title":"Am J Kidney Dis"},{"issue":"6","key":"1942_CR4","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1093\/ndt\/gfv325","volume":"31","author":"C Gast","year":"2016","unstructured":"Gast C, Pengelly RJ, Lyon M et al (2016) Collagen (COL4A) mutations are the most frequent mutations underlying adult focal segmental glomerulosclerosis. Nephrol Dial Transplant 31(6):961\u2013970. https:\/\/doi.org\/10.1093\/ndt\/gfv325","journal-title":"Nephrol Dial Transplant"},{"issue":"5","key":"1942_CR5","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1038\/ki.2013.479","volume":"85","author":"Y Hashimura","year":"2014","unstructured":"Hashimura Y, Nozu K, Kaito H et al (2014) Milder clinical aspects of X-linked Alport syndrome in men positive for the collagen IV \u03b15 chain. Kidney Int 85(5):1208\u20131213. https:\/\/doi.org\/10.1038\/ki.2013.479","journal-title":"Kidney Int"},{"issue":"7","key":"1942_CR6","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1093\/ndt\/17.7.1218","volume":"17","author":"O Gross","year":"2002","unstructured":"Gross O, Netzer KO, Lambrecht R, Seibold S, Weber M (2002) Meta-analysis of genotype-phenotype correlation in X-linked Alport syndrome: impact on clinical counselling. Nephrol Dial Transplant 17(7):1218\u20131227. https:\/\/doi.org\/10.1093\/ndt\/17.7.1218","journal-title":"Nephrol Dial Transplant"},{"issue":"7","key":"1942_CR7","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1016\/j.ekir.2020.04.011","volume":"5","author":"Y Li","year":"2020","unstructured":"Li Y, Groopman EE, D\u2019Agati V et al (2020) Type IV collagen mutations in familial IgA nephropathy. Kidney Int Rep 5(7):1075\u20131078. https:\/\/doi.org\/10.1016\/j.ekir.2020.04.011","journal-title":"Kidney Int Rep"},{"issue":"8","key":"1942_CR8","doi-asserted-by":"publisher","first-page":"2408","DOI":"10.1681\/asn.2007020241","volume":"18","author":"AD Paterson","year":"2007","unstructured":"Paterson AD, Liu XQ, Wang K et al (2007) Genome-wide linkage scan of a large family with IgA nephropathy localizes a novel susceptibility locus to chromosome 2q36. J Am Soc Nephrol 18(8):2408\u20132415. https:\/\/doi.org\/10.1681\/asn.2007020241","journal-title":"J Am Soc Nephrol"},{"key":"1942_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.938470","volume":"13","author":"X Zhou","year":"2022","unstructured":"Zhou X, Khan S, Huang D, Li L (2022) V-Set and immunoglobulin domain containing (VSIG) proteins as emerging immune checkpoint targets for cancer immunotherapy. Front Immunol 13:938470. https:\/\/doi.org\/10.3389\/fimmu.2022.938470","journal-title":"Front Immunol"}],"container-title":["Journal of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40620-024-01942-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40620-024-01942-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40620-024-01942-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T15:53:45Z","timestamp":1777564425000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/joneph\/article\/37\/3\/769\/8306648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,26]]},"references-count":9,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["1942"],"URL":"https:\/\/doi.org\/10.1007\/s40620-024-01942-7","relation":{},"ISSN":["1724-6059"],"issn-type":[{"value":"1724-6059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,26]]},"assertion":[{"value":"29 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"On behalf of all authors, the corresponding author states that there are no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed were in accordance with the ethical standards of the institute and regional committee and with the 1964 Helsinki declaration and its later amendments of comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Patient gave written consent to publish the data presented in this report.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}