{"doi":"10.1016/j.ekir.2020.04.011","title":"Type IV Collagen Mutations in Familial IgA Nephropathy","abstract":"IgA nephropathy (IgAN) is a leading cause of chronic glomerulonephritis, and exhibits highly heterogeneous clinical and pathological features1Magistroni R. D'Agati V.D. Appel G.B. Kiryluk K. New developments in the genetics, pathogenesis, and therapy of IgA nephropathy.Kidney Int. 2015; 88: 974-989Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar,2Wyatt R.J. Julian B.A. IgA nephropathy.N Engl J Med. 2013; 368: 2402-2414Crossref PubMed Scopus (647) Google Scholar. Although IgAN classically presents as a young adult with macroscopic hematuria accompanying an upper respiratory infection or gastrointestinal illness, patients can present with isolated microscopic hematuria, mild proteinuria, and/or hypertension.1Magistroni R. D'Agati V.D. Appel G.B. Kiryluk K. New developments in the genetics, pathogenesis, and therapy of IgA nephropathy.Kidney Int. 2015; 88: 974-989Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar,2Wyatt R.J. Julian B.A. IgA nephropathy.N Engl J Med. 2013; 368: 2402-2414Crossref PubMed Scopus (647) Google Scholar Diagnosis is based on renal biopsy, with characteristic features including mesangial hypercellularity and IgA-dominant deposits in the glomerular mesangium; however, diverse findings can be seen on light and electron microscopy.1Magistroni R. D'Agati V.D. Appel G.B. Kiryluk K. New developments in the genetics, pathogenesis, and therapy of IgA nephropathy.Kidney Int. 2015; 88: 974-989Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar,2Wyatt R.J. Julian B.A. IgA nephropathy.N Engl J Med. 2013; 368: 2402-2414Crossref PubMed Scopus (647) Google Scholar The prevalence of IgAN varies with ethnicity, and correspondingly follows a geographic gradient, being found most commonly in East Asians, followed by Europeans, and rarely among individuals of African descent.1Magistroni R. D'Agati V.D. Appel G.B. Kiryluk K. New developments in the genetics, pathogenesis, and therapy of IgA nephropathy.Kidney Int. 2015; 88: 974-989Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar,S1 Both such ancestry-specific variation and familial clustering of disease support that hereditary factors contribute meaningfully to the pathogenesis of IgAN; yet, although genome-wide association studies have identified many risk loci for sporadic forms of IgAN, the genetic basis of familial disease remains largely unresolved.1Magistroni R. D'Agati V.D. Appel G.B. Kiryluk K. New developments in the genetics, pathogenesis, and therapy of IgA nephropathy.Kidney Int. 2015; 88: 974-989Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar,S2 Interestingly, manifestations of IgAN, including microscopic hematuria and diffuse glomerular basement thinning,3Frasca G.M. Soverini L. Gharavi A.G. et al.Thin basement membrane disease in patients with familial IgA nephropathy.J Nephrol. 2004; 17: 778-785PubMed Google Scholar can overlap considerably with those of type IV collagen-associated nephropathy, which includes Alport syndrome (AS) and thin basement membrane disease (TBMD) and results from mutations in the COL4A3, COL4A4, and COL4A5 genes. Moreover, prior genome-wide linkage scans of familial IgAN have detected significant signals at the chromosome 2q36 region,4Paterson A.D. Liu X.Q. Wang K. et al.Genome-wide linkage scan of a large family with IgA nephropathy localizes a novel susceptibility locus to chromosome 2q36.J Am Soc Nephrol. 2007; 18: 2408-2415Crossref PubMed Scopus (90) Google Scholar which encompasses the COL4A3/A4 locus, further supporting that in some cases, type IV collagen mutations may be associated with IgAN. To investigate this hypothesis, we retrospectively analyzed the exome sequence (ES) data of 46 familial IgAN cases for putatively pathogenic COL4A3-5 variants. We report notable ES results from 12 of these 46 familial cases. These 12 families were ascertained through a proband with biopsy-proven IgAN who was referred for evaluation of familial IgAN f","journal":"Kidney International Reports","year":2020,"id":63568,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":304391,"name":"Emily Groopman","orcid":"0000-0001-8688-7551","position":1,"is_corresponding":false},{"id":240850,"name":"Vivette D. D’Agati","orcid":"0000-0001-7760-6965","position":2,"is_corresponding":false},{"id":336517,"name":"Sindhuri Prakash","orcid":"0000-0002-0277-8962","position":3,"is_corresponding":false},{"id":336518,"name":"Junying Zhang","orcid":"0000-0002-7511-0277","position":4,"is_corresponding":false},{"id":336519,"name":"Małgorzata Mizerska-Wasiak","orcid":"0000-0003-0063-8699","position":5,"is_corresponding":false},{"id":242619,"name":"Yaşar Çalışkan","orcid":"0000-0003-3816-8047","position":6,"is_corresponding":false},{"id":336520,"name":"David Fasel","orcid":"0000-0002-0815-2370","position":7,"is_corresponding":false},{"id":338199,"name":"Hussein H. Karnib","orcid":null,"position":8,"is_corresponding":false},{"id":338200,"name":"Luisa Bono","orcid":null,"position":9,"is_corresponding":false},{"id":338201,"name":"Sadek Al Omran","orcid":null,"position":10,"is_corresponding":false},{"id":338202,"name":"Essam Al Sabban","orcid":null,"position":11,"is_corresponding":false},{"id":58245,"name":"Krzysztof Kiryluk","orcid":"0000-0002-5047-6715","position":12,"is_corresponding":false},{"id":336521,"name":"Gianluca Caridi","orcid":"0000-0001-6700-3001","position":13,"is_corresponding":false},{"id":242657,"name":"Gian Marco Ghiggeri","orcid":"0000-0003-3659-9062","position":14,"is_corresponding":false},{"id":242626,"name":"Simone Sanna‐Cherchi","orcid":"0000-0002-6185-948X","position":15,"is_corresponding":false},{"id":336522,"name":"Francesco Scolari","orcid":"0000-0003-0233-9705","position":16,"is_corresponding":false},{"id":240854,"name":"Ali G. 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