{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T03:04:56Z","timestamp":1793675096093,"version":"4.5.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Unlike X-linked or autosomal recessive Alport syndrome, no clear genotype\/phenotype correlation has yet been demonstrated in patients carrying a single variant of COL4A3 or COL4A4.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We carried out a multicentre retrospective study to assess the risk factors involved in renal survival in patients presenting a single pathogenic variant on COL4A3 or COL4A4.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 97 patients presenting a single pathogenic variant of COL4A3 or COL4A4 were included. The prevalence of end-stage kidney disease (ESKD) during follow-up was 28.7% [median age 47.5\u00a0years (interquartile range 39.1\u201355.8). A total of 23 patients carried a \u2018severe\u2019 mutation (frameshift, stop gain, extensive deletion, impacting splicing) and 60 patients presented a glycine substitution in a collagenous domain. In patients with glycine missense variants, the location of the mutation in the distal exons was associated with worse renal survival with a more pronounced decline in the estimated glomerular filtration rate compared with variants in proximal exons. Conversely, the presence of a severe mutation did not impact renal survival.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our results confirm that autosomal dominant Alport syndrome (ADAS) can lead to ESKD. We demonstrated that a glycine substitution involving the distal exons had a negative impact on renal survival in ADAS patients, probably due to a trimerization defect. This could help improve personalized follow-up in ADAS patients with glycine substitution and could be integrated into a future prognostic score to accurately predict renal outcomes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfaf011","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T23:22:33Z","timestamp":1736896953000},"page":"1522-1530","source":"Crossref","is-referenced-by-count":9,"title":["Exon location of glycine substitutions impacts kidney survival in autosomal dominant Alport syndrome"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9830-640X","authenticated-orcid":false,"given":"Marie-Sophie","family":"Pagniez","sequence":"first","affiliation":[{"name":"Department of Nephrology, Kidney Transplantation and Dialysis, CHU Lille, University of Lille , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Fages","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kidney Transplantation and Dialysis, CHU Lille, University of Lille , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Gatinois","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation, Dialysis and Apheresis, CHU Bordeaux , Bordeaux ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Larrue","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, Toxicology and Genetic Diseases Department, CHU Lille , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Pottier","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, Toxicology and Genetic Diseases Department, CHU Lille , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timoth\u00e9e","family":"Laboux","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kidney Transplantation and Dialysis, CHU Lille, University of Lille , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9mi","family":"Lenain","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kidney Transplantation and Dialysis, CHU Lille, University of Lille , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Grunewald","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, Toxicology and Genetic Diseases Department, CHU Lille , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7580-0913","authenticated-orcid":false,"given":"Thomas","family":"Robert","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Kidney Transplantation, Conception Hospital, Assistance Publique-H\u00f4pitaux de Marseille , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Rigothier","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation, Dialysis and Apheresis, CHU Bordeaux , Bordeaux ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0339-3757","authenticated-orcid":false,"given":"Laurent","family":"Mesnard","sequence":"additional","affiliation":[{"name":"Service de Soins Intensifs N\u00e9phrologiques et Rein Aigu, French Intensive Renal Network, Tenon Hospital, Assistance Publique-H\u00f4pitaux de Paris , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Glowacki","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kidney Transplantation and Dialysis, CHU Lille, University of Lille , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"2025080112222317200_bib1","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1038\/ejhg.2014.254","article-title":"Clinical utility gene card for: Alport syndrome \u2013 update 2014","volume":"23","author":"Hertz","year":"2015","journal-title":"Eur J Hum Genet"},{"key":"2025080112222317200_bib2","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.1681\/ASN.2020071065","article-title":"Prevalence estimates of predicted pathogenic COL4A3-COL4A5 variants in a population sequencing database and their implications for Alport syndrome","volume":"32","author":"Gibson","year":"2021","journal-title":"J Am Soc Nephrol"},{"key":"2025080112222317200_bib3","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1093\/ndt\/gfac163","article-title":"Alport syndrome and autosomal dominant tubulointerstitial kidney disease frequently underlie end-stage renal disease of unknown origin\u2014a single-center analysis","volume":"37","author":"Leenen","year":"2022","journal-title":"Nephrol Dial Transplant"},{"key":"2025080112222317200_bib4","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1681\/ASN.V12197","article-title":"Structure of the human type IV collagen gene COL4A3 and mutations in autosomal Alport syndrome","volume":"12","author":"Heidet","year":"2001","journal-title":"J Am Soc Nephrol"},{"key":"2025080112222317200_bib5","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1073\/pnas.87.4.1606","article-title":"Identification of a distinct type IV collagen alpha chain with restricted kidney distribution and assignment of its gene to the locus of X chromosome-linked Alport syndrome","volume":"87","author":"Hostikka","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025080112222317200_bib6","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.matbio.2016.08.005","article-title":"Collagen IV diseases: a focus on the glomerular basement membrane in Alport syndrome","volume":"57\u20138","author":"Cosgrove","year":"2017","journal-title":"Matrix Biol"},{"key":"2025080112222317200_bib7","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.1172\/JCI118241","article-title":"Comparative distribution of the alpha 1(IV), alpha 5(IV), and alpha 6(IV) collagen chains in normal human adult and fetal tissues and in kidneys from X-linked Alport syndrome patients","volume":"96","author":"Peissel","year":"1995","journal-title":"J Clin Invest"},{"key":"2025080112222317200_bib8","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1038\/s41431-021-00858-1","article-title":"Consensus statement on standards and guidelines for the molecular diagnostics of Alport syndrome: refining the ACMG criteria","volume":"29","author":"Savige","year":"2021","journal-title":"Eur J Hum Genet"},{"key":"2025080112222317200_bib9","doi-asserted-by":"publisher","first-page":"31142","DOI":"10.1074\/jbc.M201740200","article-title":"Crystal structure of NC1 domains. 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