{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:50:23Z","timestamp":1782301823175,"version":"3.54.5"},"reference-count":26,"publisher":"Gobierno de Navarra","issue":"1","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-sa\/4.0\/deed.es"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["An Sist Sanit Navar"],"abstract":"<jats:p>Autosomal dominant Alport syndrome (ADAS) is the least common form of Alport syndrome, the second most common monogenic cause of chronic kidney disease after autosomal dominant polycystic kidney disease.\nWe report a 14-year follow-up of a patient with ADAS carrying a likely pathogenic heterozygous variant in COL4A3 (Gly366Arg substitution). The disease initially presented with microhematuria and no renal impairment on analysis or ultrasound. The patient progressively developed bilateral renal cysts and renal failure -a classic renal pattern of the syndrome- and bilateral hearing loss. Incidentally, infertility study (had not children) showed teratozoospermia and elevated levels of luteinizing hormone and progesterone, hormones associated with spermatogenesis. Long-term follow-up of rare variants of Alport syndrome helps refine genotype\u2013phenotype correlations and disease progression. The incidental finding of teratozoospermia raises the possibility of an etiological association, that warrants further investigation as \u03b13(IV) collagen chains involved in spermatogenesis are present in seminiferous tubules.<\/jats:p>","DOI":"10.23938\/assn.1158","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T12:44:23Z","timestamp":1776689063000},"page":"e1158","source":"Crossref","is-referenced-by-count":0,"title":["Phenotype of autosomal dominant Alport syndrome with a likely pathogenic heterozygous variant in the COL4A3 gene (Gly366Arg) and incidental teratozoospermia: A case report","Fenotipo de s\u00edndrome de Alport autos\u00f3mico dominante con variante probablemente patog\u00e9nica del gen COL4A3 (Gly366Arg) en heterocigosis y teratozoospermia incidental: Caso cl\u00ednico"],"prefix":"10.23938","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4757-2930","authenticated-orcid":false,"given":"Vicente","family":"Mart\u00edn Moreno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Mart\u00edn Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asunci\u00f3n","family":"Garc\u00eda Mateos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Hurtado Gallar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6311-7175","authenticated-orcid":false,"given":"Cristina","family":"Angulo Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5731-7055","authenticated-orcid":false,"given":"Raquel","family":"S\u00e1nchez-Redondo Mayordomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10024","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"1.- BAROCAS DA, BOORJIAN SA, ALVAREZ RD, DOWNS TM, GROSS CP, HAMILTON BD et al. Microhematuria: AUA\/SUFU Guideline. J Urol 2020;204(4):778-786. https:\/\/doi.org\/10.1097\/ju.0000000000001297","DOI":"10.1097\/JU.0000000000001297"},{"key":"ref1","doi-asserted-by":"publisher","unstructured":"2.- LINDER BJ, BASS EJ, MOSTAFID H, BOORJIAN SA. Guideline of guidelines: Asymptomatic microscopic haematuria. BJU Int 2018;121(2):176-183. https:\/\/doi.org\/10.1111\/bju.14016","DOI":"10.1111\/bju.14016"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"3.- JOUKAR F, HASSANIPOUR S, ATEFI A, MAROUFIZADEH S, AKHAVAN A, NAGHIPOUR M et al. Prevalence and associated factors for asymptomatic microscopic hematuria in adults in the PERSIAN Guilan cohort study (PGCS). Sci Rep 2024;14(1):3452. https:\/\/doi.org\/10.1038\/s41598-024-53597-w","DOI":"10.1038\/s41598-024-53597-w"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"4.- L\u00d6BIG N, WEZEL F, MARTINI T, SCHR\u00d6PPEL B, BOLENZ C. [Microscopic hematuria: Reasonable and risk-adapted diagnostic evaluation]. Urologe A 2017;56(9):1139-1146. https:\/\/doi.org\/10.1007\/s00120-017-0432-2","DOI":"10.1007\/s00120-017-0432-2"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"5.- TORRA R, LIPSKA-ZI\u0118TKIEWICZ B, ACKE F, ANTIGNAC C, BECKER JU, CORNEC-LE GALL E et al. ERKNet, ERA Genes&Kidney and ESPN Inherited renal disorders working group. Diagnosis, management and treatment of the Alport syndrome - 2024 guideline on behalf of ERKNet, ERA and ESPN. Nephrol Dial Transplant 2025;40(6):1091-1106. https:\/\/doi.org\/10.1093\/ndt\/gfae265","DOI":"10.1093\/ndt\/gfae265"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"6.- KASHTAN CE, DING J, GAROSI G, HEIDET L, MASSELLA L, NAKANISHI K et al. Alport syndrome: a unified classification of genetic disorders of collagen IV \u03b1345: a position paper of the Alport Syndrome Classification Working Group. Kidney Int 2018;93(5):1045-1051. https:\/\/doi.org\/10.1016\/j.kint.2017.12.018","DOI":"10.1016\/j.kint.2017.12.018"},{"key":"ref6","unstructured":"7.- NOZU K, YAMAMURA T, HORINOUCHI T. Alport Syndrome. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews Seattle (WA): University of Washington, 2001 (actualizado el 27 de febrero de 2025); 1993-2025. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1207\/"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"8.- VIVANTE A. Genetics of Chronic Kidney Disease. N Engl J Med 2024;391(7):627-639. https:\/\/doi.org\/10.1056\/nejmra2308577","DOI":"10.1056\/NEJMra2308577"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"9.- ZENI L, MESCIA F, TOSO D, DORDONI C, MAZZA C, SAVOLDI G et al. Clinical Significance of the Cystic Phenotype in Alport Syndrome. Am J Kidney Dis 2024;84(3):320-328.e1. https:\/\/doi.org\/10.1053\/j.ajkd.2024.02.005","DOI":"10.1053\/j.ajkd.2024.02.005"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"10.- FURLANO M, MART\u00cdNEZ V, PYBUS M, ARCE Y, CRESP\u00cd J, VENEGAS MDP et al. Clinical and genetic features of autosomal dominant Alport syndrome: A cohort study. Am J Kidney Dis 2021;78(4):560-570.e1. https:\/\/doi.org\/10.1053\/j.ajkd.2021.02.326","DOI":"10.1053\/j.ajkd.2021.02.326"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"11.- SOLANKI KV, HU Y, MOORE BS, ABEDI V, AVULA V, MIRSHAHI T; Regeneron Genetics Center; Strande NT, Bucaloiu ID, Chang AR. The Phenotypic Spectrum of COL4A3 heterozygotes. Kidney Int Rep 2023;8(10):2088-2099. https:\/\/doi.org\/10.1016\/j.ekir.2023.07.010","DOI":"10.1016\/j.ekir.2023.07.010"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"12.- GIBSON JT, HUANG M, SHENELLI CROOS DABRERA M, SHUKLA K, ROTHE H, HILBERT P et al. Genotype-phenotype correlations for COL4A3-COL4A5 variants resulting in Gly substitutions in Alport syndrome. Sci Rep 2022;12(1):2722. https:\/\/doi.org\/10.1038\/s41598-022-06525-9","DOI":"10.1038\/s41598-022-06525-9"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"13.- COUTTON C, ESCOFFIER J, MARTINEZ G, ARNOULT C, RAY PF. Teratozoospermia: spotlight on the main genetic actors in the human. Hum Reprod Update 2015;21(4):455-485. https:\/\/doi.org\/10.1093\/humupd\/dmv020","DOI":"10.1093\/humupd\/dmv020"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"14.- GARC\u00cdA-AZNAR JM, DE LA HIGUERA L, BESADA CERECEDO L, GANDIAGA NP, VEGA AI, FERN\u00c1NDEZ-FRESNEDO G et al. New insights into renal failure in a cohort of 317 patients with autosomal dominant forms of alport syndrome: Report of two novel heterozygous mutations in COL4A3. J Clin Med 2022;11(16):4883. https:\/\/doi.org\/10.1093\/humupd\/dmv020","DOI":"10.1093\/humupd\/dmv020"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"15.- HU N, SUN L, DAI X, ZHAO Z, ZHANG X, RAO J et al. Age at disease onset and risk of chronic kidney disease in patients with heterozygous disease-causing variants in COL4A3 and COL4A4. Clin Kidney J 2025;18(10):sfaf272. https:\/\/doi.org\/10.1093\/ckj\/sfaf272","DOI":"10.1093\/ckj\/sfaf272"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"16.- PAGNIEZ MS, LOMBARDI Y, FAGES V, LARRUE R, LABOUX T, GATINOIS C et al. Challenging the narrative of Alport syndrome spectrum: No link with cystic phenotype. Nephrol Dial Transplant 2025;40(7):1408-1415. https:\/\/doi.org\/10.1093\/ckj\/sfaf272","DOI":"10.1093\/ckj\/sfaf272"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"17.- FURLANO M, PILCO-TERAN M, PYBUS M, MART\u00cdNEZ V, AZA-CARMONA M, RIUS PERIS A et al. Increased prevalence of kidney cysts in individuals carrying heterozygous COL4A3 or COL4A4 pathogenic variants. Nephrol Dial Transplant 2024;39(9):1442-1448. https:\/\/doi.org\/10.1093\/ndt\/gfae031","DOI":"10.1093\/ndt\/gfae031"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"18.- CASTELLINI C, CORDESCHI G, TIENFORTI D, BARBONETTI A. Relationship between male aging and semen quality: A retrospective study on over 2500 men. Arch Gynecol Obstet 2024;309(6):2843-2852. https:\/\/doi.org\/10.1007\/s00404-024-07448-8","DOI":"10.1007\/s00404-024-07448-8"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"19.- LIU SW, LI HT, GE RS, CHENG CY. NC1-peptide derived from collagen \u03b13 (IV) chain is a blood-tissue barrier regulator: Lesson from the testis. Asian J Androl 2021;23(2):123-128. https:\/\/doi.org\/10.4103\/aja.aja_44_20","DOI":"10.4103\/aja.aja_44_20"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"20.- LIU S, LI H, WU S, LI L, GE R, CHENG CY. NC1-peptide regulates spermatogenesis through changes in cytoskeletal organization mediated by EB1. FASEB J 2020;34(2):3105-3128. https:\/\/doi.org\/10.1096\/fj.201901968rr","DOI":"10.1096\/fj.201901968RR"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"21.- HARVEY SJ, PERRY J, ZHENG K, CHEN D, SADO Y, JEFFERSON B et al. Sequential expression of type IV collagen networks: testis as a model and relevance to spermatogenesis. Am J Pathol 2006;168(5):1587-1597. https:\/\/doi.org\/10.2353\/ajpath.2006.050816","DOI":"10.2353\/ajpath.2006.050816"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"22.- KAHSAI TZ, ENDERS GC, GUNWAR S, BRUNMARK C, WIESLANDER J, KALLURI R et al. Seminiferous tubule basement membrane. Composition and organization of type IV collagen chains, and the linkage of alpha3(IV) and alpha5(IV) chains. J Biol Chem 1997;272(27):17023-17032. https:\/\/doi.org\/10.1074\/jbc.272.27.17023","DOI":"10.1074\/jbc.272.27.17023"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"23.- WU X, GAO S, WANG L, BU T, WU S, ZHOU L et al. Role of laminin and collagen chains in human spermatogenesis - Insights from studies in rodents and scRNA-Seq transcriptome profiling. Semin Cell Dev Biol 2022;121:125-132. https:\/\/doi.org\/10.1016\/j.semcdb.2021.07.011","DOI":"10.1016\/j.semcdb.2021.07.011"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"24.- ERDO\u011cRU T, G\u00dcLKESEN KH, BAH\u00c7ECI M, KARPUZO\u011cLU G, BAYKARA M. The role of expression of extracellular matrix proteins and epidermal growth factor receptor activity on fertilization capacity of testicular harvested spermatozoa. Andrologia 2002;34(2):98-106. https:\/\/doi.org\/10.1046\/j.0303-4569.2001.00482.x","DOI":"10.1046\/j.0303-4569.2001.00482.x"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"25.- NETZER KO, SUZUKI K, ITOH Y, HUDSON BG, KHALIFAH RG. Comparative analysis of the noncollagenous NC1 domain of type IV collagen: Identification of structural features important for assembly, function, and pathogenesis. Protein Sci 1998;7(6):1340-1351. https:\/\/doi.org\/10.1002\/pro.5560070610","DOI":"10.1002\/pro.5560070610"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"26.- ATMOKO W, SAVIRA M, SHAH R, CHUNG E, AGARWAL A. Isolated teratozoospermia: Revisiting its relevance in male infertility: A narrative review. Transl Androl Urol 2024;13(2):260-273. https:\/\/doi.org\/10.21037\/tau-23-397","DOI":"10.21037\/tau-23-397"}],"container-title":["Anales del Sistema Sanitario de Navarra"],"original-title":[],"link":[{"URL":"https:\/\/recyt.fecyt.es\/index.php\/ASSN\/article\/download\/119156\/87617","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/recyt.fecyt.es\/index.php\/ASSN\/article\/download\/119156\/87617","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:26:12Z","timestamp":1782300372000},"score":1,"resource":{"primary":{"URL":"https:\/\/recyt.fecyt.es\/index.php\/ASSN\/article\/view\/119156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,2,10]]}},"URL":"https:\/\/doi.org\/10.23938\/assn.1158","relation":{},"ISSN":["2340-3527","1137-6627"],"issn-type":[{"value":"2340-3527","type":"electronic"},{"value":"1137-6627","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4,20]]}}}