{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:35:29Z","timestamp":1768512929325,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,3,13]],"date-time":"2011-03-13T00:00:00Z","timestamp":1299974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>Demosthenous P, Voskarides K, Stylianou K, Hadjigavriel M, Arsali M, Patsias C, Georgaki E, Zirogiannis P, Stavrou C, Daphnis E, Pierides A, Deltas C, Hellenic Nephrogenetics Research Consortium. X\u2010linked Alport syndrome in Hellenic families: Phenotypic heterogeneity and mutations near interruptions of the collagen domain in <jats:italic>COL4A5<\/jats:italic>.<\/jats:p><jats:p>The X\u2010linked Alport syndrome (ATS) is caused by mutations in <jats:italic>COL4A5<\/jats:italic> and exhibits a widely variable expression. Usually ATS is heralded with continuous microhematuria which rapidly progresses to proteinuria, hypertension and chronic or end\u2010stage renal disease (ESRD) by adolescence, frequently accompanied by sensorineural deafness and ocular complications. Milder forms of ATS also exist. We studied 42 patients (19M, 23F) of nine Hellenic families suspected clinically of X\u2010linked ATS who presented with marked phenotypic heterogeneity. We identified mutations in <jats:italic>COL4A5<\/jats:italic> in six families. Two males with nonsense mutation E228X reached ESRD by ages 14 and 18. Frameshift mutation 2946delT followed the same course with early onset renal involvement and deafness. However, two males with the milder missense mutation G624D, reached ESRD after 39 years and one patient showed thin basement membrane nephropathy (TBMN). Another 5\/8 affected males with missense mutation P628L also developed ESRD between 30 and 57 years, while three exhibit only mild chronic renal failure (CRF). The data support previous findings that certain mutations are associated with milder phenotypes and confirm that mutation G624D may be expressed as TBMN with familial hematuria. Similar conclusions apply for missense mutation P628L. Interestingly, mutations G624D and P628L are near the 12th natural interruption of <jats:italic>COL4A5<\/jats:italic> triple helical domain, which may explain the milder phenotype.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2011.01647.x","type":"journal-article","created":{"date-parts":[[2011,2,17]],"date-time":"2011-02-17T09:51:17Z","timestamp":1297936277000},"page":"240-248","source":"Crossref","is-referenced-by-count":38,"title":["X\u2010linked Alport syndrome in Hellenic families: Phenotypic heterogeneity and mutations near interruptions of the collagen domain in <i>COL4A5<\/i>"],"prefix":"10.1111","volume":"81","author":[{"given":"P","family":"Demosthenous","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Voskarides","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Stylianou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Hadjigavriel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Arsali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Patsias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Georgaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Zirogiannis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Stavrou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Daphnis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Pierides","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Deltas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Hellenic Nephrogenetics Research Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,3,13]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(61)90899-6"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.3454.504"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1985.63"},{"key":"e_1_2_7_5_2","first-page":"249","article-title":"Mapping of Alport syndrome to the long arm of the X chromosome.","volume":"42","author":"Atkin CL","year":"1988","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2349482"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0994-77"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000101802"},{"key":"e_1_2_7_9_2","doi-asserted-by":"crossref","first-page":"224","DOI":"10.5858\/133.2.224","article-title":"Alport syndrome and thin glomerular basement membrane nephropathy: a practical approach to diagnosis.","volume":"133","author":"Haas M.","year":"2009","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.ndt.a027677"},{"key":"e_1_2_7_11_2","first-page":"S20","article-title":"Alport's syndrome: experience at Hopital Necker.","volume":"11","author":"Habib R","year":"1982","journal-title":"Kidney Int Suppl"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004670050699"},{"key":"e_1_2_7_13_2","first-page":"239","article-title":"[Thin basement membrane nephropathy: a mutation in COL4A5 gene].","volume":"40","author":"Chen Y","year":"2001","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002221"},{"key":"e_1_2_7_15_2","first-page":"15","article-title":"Genetic, clinical, and morphologic heterogeneity in Alport's syndrome.","volume":"22","author":"Gubler MC","year":"1993","journal-title":"Adv Nephrol Necker Hosp"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00601.x"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000090034.71205.74"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.7.1218"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfl394"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009070784"},{"key":"e_1_2_7_21_2","doi-asserted-by":"crossref","first-page":"12475","DOI":"10.1016\/S0021-9258(18)42301-0","article-title":"Complete amino acid sequence of the human alpha 5 (IV) collagen chain and identification of a single\u2010base mutation in exon 23 converting glycine 521 in the collagenous domain to cysteine in an Alport syndrome patient.","volume":"267","author":"Zhou J","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_2_7_22_2","doi-asserted-by":"crossref","first-page":"6608","DOI":"10.1016\/S0021-9258(17)37416-1","article-title":"Structure of the human type IV collagen COL4A5 gene.","volume":"269","author":"Zhou J","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00299-001-0399-7"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfm024"},{"key":"e_1_2_7_26_2","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1681\/ASN.V9122291","article-title":"High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing.","volume":"9","author":"Martin P","year":"1998","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20010115)98:2<148::AID-AJMG1024>3.0.CO;2-W"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007040444"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp158"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfn635"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfn779"},{"key":"e_1_2_7_32_2","unstructured":"PieridesA ArsaliA AthanasiouYDeltasC.et al.Familial late onset FSGS leading to proteinuria CRF and ESRD in patients with heterozygous COL4A3\/COL4A4 mutations thin glomerular basement membranes and familial microscopic hematuria. Results from 166 patients in 16 large family pedigrees.San Diego:Renal week of American Society of Nephrologists 2009."},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-010-1484-3"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0671"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1080\/03008200802148280"},{"key":"e_1_2_7_36_2","first-page":"1157","article-title":"A mutation causing Alport syndrome with tardive hearing loss is common in the western United States.","volume":"58","author":"Barker DF","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-009-1370-z"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.11.075"},{"key":"e_1_2_7_39_2","unstructured":"DeltasC.Inherited diseases and cyprus reality. A historico\u2010genetic approach. In the 30th Annals of the Cyprus Research Center (Epetirida).Nicosia Cyprus:Ministry of Education and Culture 2004."}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-0004.2011.01647.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-0004.2011.01647.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T01:07:03Z","timestamp":1698714423000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-0004.2011.01647.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,13]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["10.1111\/j.1399-0004.2011.01647.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-0004.2011.01647.x","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,13]]}}}