{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:23:16Z","timestamp":1791274996316,"version":"4.1.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>\n                      Genetic heterogeneity and phenotypic variability are major challenges in familial nephronophthisis and related ciliopathies. To date, mutations in 20 different genes (\n                      <jats:italic toggle=\"yes\">NPHP1<\/jats:italic>\n                      to\n                      <jats:italic toggle=\"yes\">-20<\/jats:italic>\n                      ) have been identified causing either isolated kidney disease or complex multiorgan disorders. In this study, we provide a comprehensive and detailed characterization of 152 children with a special focus on extrarenal organ involvement and the long-term development of ESRD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>We established an online-based registry (www.nephreg.de) to assess the clinical course of patients with nephronophthisis and related ciliopathies on a yearly base. Cross-sectional and longitudinal data were collected. Mean observation time was 7.5\u00b16.1 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 51% of the children presented with isolated nephronophthisis, whereas the other 49% exhibited related ciliopathies. Monogenetic defects were identified in 97 of 152 patients, 89 affecting\n                      <jats:italic toggle=\"yes\">NPHP<\/jats:italic>\n                      genes. Eight patients carried mutations in other genes related to cystic kidney diseases. A homozygous\n                      <jats:italic toggle=\"yes\">NPHP1<\/jats:italic>\n                      deletion was, by far, the most frequent genetic defect (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =60). We observed a high prevalence of extrarenal manifestations (23% [14 of 60] for the\n                      <jats:italic toggle=\"yes\">NPHP1<\/jats:italic>\n                      group and 66% [61 of 92] for children without\n                      <jats:italic toggle=\"yes\">NPHP1<\/jats:italic>\n                      ). A homozygous\n                      <jats:italic toggle=\"yes\">NPHP1<\/jats:italic>\n                      deletion not only led to juvenile nephronophthisis but also was able to present as a predominantly neurologic phenotype. However, irrespective of the initial clinical presentation, the kidney function of all patients carrying\n                      <jats:italic toggle=\"yes\">NPHP1<\/jats:italic>\n                      mutations declined rapidly between the ages of 8 and 16 years, with ESRD at a mean age of 11.4\u00b12.4 years. In contrast within the non-\n                      <jats:italic toggle=\"yes\">NPHP1<\/jats:italic>\n                      group, there was no uniform pattern regarding the development of ESRD comprising patients with early onset and others preserving normal kidney function until adulthood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Mutations in\n                      <jats:italic toggle=\"yes\">NPHP<\/jats:italic>\n                      genes cause a wide range of ciliopathies with multiorgan involvement and different clinical outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.01280217","type":"journal-article","created":{"date-parts":[[2017,11,16]],"date-time":"2017-11-16T20:25:43Z","timestamp":1510863943000},"page":"1974-1983","source":"Crossref","is-referenced-by-count":108,"title":["Phenotypic Spectrum of Children with Nephronophthisis and Related Ciliopathies"],"prefix":"10.2215","volume":"12","author":[{"given":"Jens","family":"K\u00f6nig","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta","family":"Kranz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"K\u00f6nig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl 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the Gesellschaft f\u00fcr P\u00e4diatrische Nephrologie (GPN)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,11,16]]},"reference":[{"key":"B2-20230813","first-page":"1","article-title":"[Familial, juvenile nephronophthisis (idiopathic parenchymal contracted kidney)]","volume":"6","author":"Fanconi","year":"1951","journal-title":"Helv Paediatr Acta"},{"key":"B3-20230813","first-page":"369","article-title":"Congenital medullary cysts of the kidneys with severe refractory anemia.","volume":"69","author":"Smith","year":"1945","journal-title":"Am J Dis Child"},{"key":"B4-20230813","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.gde.2005.04.012","article-title":"Nephronophthisis.","volume":"15","author":"Saunier","year":"2005","journal-title":"Curr Opin Genet 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Mutat"},{"key":"B43-20230813","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/ng1805","article-title":"Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome.","volume":"38","author":"Valente","year":"2006","journal-title":"Nat Genet"},{"key":"B44-20230813","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/ng.97","article-title":"Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome.","volume":"40","author":"Leitch","year":"2008","journal-title":"Nat Genet"},{"key":"B45-20230813","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1007\/s00431-011-1553-z","article-title":"Educational paper: Ciliopathies.","volume":"171","author":"Bergmann","year":"2012","journal-title":"Eur J Pediatr"},{"key":"B46-20230813","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1136\/jmg.2009.066613","article-title":"Hypomorphic mutations in meckelin (MKS3\/TMEM67) cause 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