{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:22:14Z","timestamp":1790878934261,"version":"4.1.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>\n                      Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in\n                      <jats:italic toggle=\"yes\">collagen 4A3<\/jats:italic>\n                      and\/or\n                      <jats:italic toggle=\"yes\">collagen 4A4<\/jats:italic>\n                      accounts for &lt;5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective analysis of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (a total of 72 patients) from 16 unrelated families. Patients with suspected Alport syndrome after pathologic examination who were referred from anywhere in Japan for genetic analysis from 2006 to 2015 were included in this study. Clinical, laboratory, and pathologic data were collected from medical records at the point of registration for genetic diagnosis. Genetic analysis was performed by targeted resequencing of 27 podocyte-related genes, including Alport\u2013related\n                      <jats:italic toggle=\"yes\">collagen<\/jats:italic>\n                      genes, to make a diagnosis of autosomal dominant Alport syndrome and identify modifier genes or double mutations. Clinical data were obtained from medical records.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median renal survival time was 70 years, and the median age at first detection of proteinuria was 17 years old. There was one patient with hearing loss and one patient with ocular lesion. Among 16 patients who underwent kidney biopsy, three showed FSGS, and seven showed thinning without lamellation of the glomerular basement membrane. Five of 13 detected mutations were reported to be causative mutations for autosomal recessive Alport syndrome in previous studies. Two families possessed double mutations in both\n                      <jats:italic toggle=\"yes\">collagen 4A3<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">collagen 4A4<\/jats:italic>\n                      , but no modifier genes were detected among the other podocyte\u2013related genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The renal phenotype of autosomal dominant Alport syndrome was much milder than that of autosomal recessive Alport syndrome or X\u2013linked Alport syndrome in men. It may, thus, be difficult to make an accurate diagnosis of autosomal dominant Alport syndrome on the basis of clinical or pathologic findings. No modifier genes were identified among the known podocyte\u2013related genes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.01000116","type":"journal-article","created":{"date-parts":[[2016,6,8]],"date-time":"2016-06-08T23:27:25Z","timestamp":1465428445000},"page":"1441-1449","source":"Crossref","is-referenced-by-count":121,"title":["Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome"],"prefix":"10.2215","volume":"11","author":[{"given":"Naohiro","family":"Kamiyoshi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandai","family":"Nozu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue Jun","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Morisada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimi","family":"Nozu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Juan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Imafuku","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Toranomon Hospital, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Tokyo, Tokyo, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Minamikawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akemi","family":"Shono","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Ninchoji","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Morioka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wakayama Medical University, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norishige","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wakayama Medical University, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kaito","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumoto","family":"Iijima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,6,8]]},"reference":[{"key":"B1-20230816","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1038\/ki.1996.459","article-title":"Alport syndrome.","volume":"50","author":"Kashtan","year":"1996","journal-title":"Kidney Int"},{"key":"B2-20230816","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1093\/ndt\/gfm024","article-title":"Alport syndrome and the X chromosome: Implications of a diagnosis of Alport syndrome in females.","volume":"22","author":"Kashtan","year":"2007","journal-title":"Nephrol Dial Transplant"},{"key":"B3-20230816","doi-asserted-by":"crossref","first-page":"e115015","DOI":"10.1371\/journal.pone.0115015","article-title":"Frequency of COL4A3\/COL4A4 mutations amongst families segregating glomerular microscopic hematuria and evidence for activation of the unfolded protein response. 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sequencing.","volume":"25","author":"Morini\u00e8re","year":"2014","journal-title":"J Am Soc Nephrol"},{"key":"B7-20230816","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1093\/ndt\/16.10.2008","article-title":"Identification of a new mutation in the alpha4(IV) collagen gene in a family with autosomal dominant Alport syndrome and hypercholesterolaemia.","volume":"16","author":"Ciccarese","year":"2001","journal-title":"Nephrol Dial Transplant"},{"key":"B8-20230816","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1093\/ndt\/12.8.1595","article-title":"Autosomal dominant Alport syndrome linked to the type IV collage alpha 3 and alpha 4 genes (COL4A3 and COL4A4).","volume":"12","author":"Jefferson","year":"1997","journal-title":"Nephrol Dial Transplant"},{"key":"B9-20230816","first-page":"320","article-title":"Autosomal dominant Alport\u2019s syndrome: Study of a large Tunisian family.","volume":"17","author":"Kharrat","year":"2006","journal-title":"Saudi J Kidney Dis Transpl"},{"key":"B10-20230816","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1093\/ndt\/gfn681","article-title":"Autosomal dominant Alport syndrome: Molecular analysis of the COL4A4 gene and clinical outcome.","volume":"24","author":"Marcocci","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"B11-20230816","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1111\/j.1523-1755.2004.00560.x","article-title":"Autosomal-dominant Alport syndrome: Natural history of a disease due to COL4A3 or COL4A4 gene.","volume":"65","author":"Pescucci","year":"2004","journal-title":"Kidney Int"},{"key":"B12-20230816","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1111\/j.1523-1755.2000.00358.x","article-title":"Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation.","volume":"58","author":"van der Loop","year":"2000","journal-title":"Kidney Int"},{"key":"B13-20230816","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1542\/peds.58.2.259","article-title":"A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine.","volume":"58","author":"Schwartz","year":"1976","journal-title":"Pediatrics"},{"key":"B14-20230816","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/S0022-3476(85)80697-1","article-title":"A simple estimate of glomerular filtration rate in adolescent boys.","volume":"106","author":"Schwartz","year":"1985","journal-title":"J Pediatr"},{"key":"B15-20230816","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1053\/j.ajkd.2008.12.034","article-title":"Revised equations for estimated GFR from serum creatinine in Japan.","volume":"53","author":"Matsuo","year":"2009","journal-title":"Am J Kidney Dis"},{"key":"B16-20230816","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1038\/ki.2013.479","article-title":"Milder clinical aspects of X-linked Alport syndrome in men positive for the collagen IV \u03b15 chain.","volume":"85","author":"Hashimura","year":"2014","journal-title":"Kidney Int"},{"key":"B17-20230816","doi-asserted-by":"crossref","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":"B18-20230816","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1007\/s00467-014-2797-4","article-title":"Natural history of genetically proven autosomal recessive Alport syndrome.","volume":"29","author":"Oka","year":"2014","journal-title":"Pediatr Nephrol"},{"key":"B19-20230816","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1681\/ASN.V114649","article-title":"X-linked Alport syndrome: Natural history in 195 families and genotype- phenotype correlations in 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are the most frequent mutations underlying adult focal segmental glomerulosclerosis [published online ahead of print September 7, 2015].","author":"Gast","journal-title":"Nephrol Dial Transplant"},{"key":"B23-20230816","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1136\/jmedgenet-2014-102822","article-title":"Evidence of digenic inheritance in Alport syndrome.","volume":"52","author":"Mencarelli","year":"2015","journal-title":"J Med Genet"},{"key":"B24-20230816","doi-asserted-by":"crossref","first-page":"4236","DOI":"10.1093\/ndt\/gfs468","article-title":"COL4A5-associated X-linked Alport syndrome in a female patient with early inner ear deafness due to a mutation in MYH9.","volume":"27","author":"Strasser","year":"2012","journal-title":"Nephrol Dial Transplant"}],"container-title":["Clinical Journal of the American Society of 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