{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:11:47Z","timestamp":1777417907328,"version":"3.51.4"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,3,26]],"date-time":"2014-03-26T00:00:00Z","timestamp":1395792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Dutch Kidney Foundation","doi-asserted-by":"crossref","award":["KJPB09.009"],"award-info":[{"award-number":["KJPB09.009"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002997","name":"Dutch Kidney Foundation","doi-asserted-by":"crossref","award":["IP11.58"],"award-info":[{"award-number":["IP11.58"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002997","name":"Dutch Kidney Foundation","doi-asserted-by":"crossref","award":["CP11.18"],"award-info":[{"award-number":["CP11.18"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001826","name":"The Netherlands Organization for Health Research and Development","doi-asserted-by":"crossref","award":["ZonMW Veni-91612095"],"award-info":[{"award-number":["ZonMW Veni-91612095"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001826","name":"The Netherlands Organization for Health Research and Development","doi-asserted-by":"crossref","award":["ZonMW Veni-91613008"],"award-info":[{"award-number":["ZonMW Veni-91613008"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Netherlands Organization for Scientific Research","award":["NWO Vidi-91786396"],"award-info":[{"award-number":["NWO Vidi-91786396"]}]},{"name":"The Netherlands Organization for Scientific Research","award":["Vici-016130664"],"award-info":[{"award-number":["Vici-016130664"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec><jats:label\/><jats:p>Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that is the most frequent monogenic cause of end\u2010stage renal disease in children. Infantile NPHP, often in combination with other features like <jats:italic>situs inversus<\/jats:italic>, are commonly caused by mutations in the <jats:italic>INVS<\/jats:italic> gene. <jats:italic>INVS<\/jats:italic> encodes the ciliary protein inversin, and mutations induce dysfunction of the primary cilia. In this article, we present a family with two severely affected fetuses that were aborted after discovery of grossly enlarged cystic kidneys by ultrasonography before 22 weeks gestation. Exome sequencing showed that the fetuses were homozygous for a previously unreported nonsense mutation, resulting in a truncation in the IQ1 domain of inversin. This mutation induces nonsense\u2010mediated RNA decay, as suggested by a reduced RNA level in fibroblasts derived from the fetus. However, a significant amount of mutant <jats:italic>INVS<\/jats:italic> RNA was present in these fibroblasts, yielding mutant inversin protein that was mislocalized. In control fibroblasts, inversin was present in the ciliary axoneme as well as at the basal body, whereas in the fibroblasts from the fetus, inversin could only be detected at the basal body. The phenotype of both fetuses is partly characteristic of infantile NPHP and Potter sequence. We also identified that the fetuses had mild skeletal abnormalities, including shortening and bowing of long bones, which may expand the phenotypic spectrum associated with <jats:italic>INVS<\/jats:italic> mutations. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36501","type":"journal-article","created":{"date-parts":[[2014,3,26]],"date-time":"2014-03-26T17:48:36Z","timestamp":1395856116000},"page":"1627-1634","source":"Crossref","is-referenced-by-count":7,"title":["Early presentation of cystic kidneys in a family with a homozygous <i>INVS<\/i> mutation"],"prefix":"10.1002","volume":"164","author":[{"given":"Machteld M.","family":"Oud","sequence":"first","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Radboud Institute for Health Sciences Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences Radboud University Nijmegen Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bregje W.","family":"van Bon","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernie M. H. F.","family":"Bongers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Hoischen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences Radboud University Nijmegen Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo L.","family":"Marcelis","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"de Leeuw","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Radboud Institute for Health Sciences Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences Radboud University Nijmegen Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne J. J.","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Pathology Jeroen Bosch Hospital \u2018s\u2010Hertogenbosch The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geert","family":"Mortier","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Antwerp University Hospital and University of Antwerp Edegem Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nine V. A. M.","family":"Knoers","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Centre Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han G.","family":"Brunner","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Radboud Institute for Health Sciences Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences Radboud University Nijmegen Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Roepman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Radboud Institute for Health Sciences Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences Radboud University Nijmegen Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heleen H.","family":"Arts","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Radboud Institute for Health Sciences Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences Radboud University Nijmegen Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,3,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2069"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-012-2259-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.01.015"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.284"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr280"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03256458"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000331273"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00859626"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.08.004"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/302108"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1297-0"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1727"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.581"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.868"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31336"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000320888"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2011.11.012"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1217"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2005.04.012"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.037408"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1552"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(74)80753-5"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.662"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.36501","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.36501","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36501","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T23:33:16Z","timestamp":1696548796000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,26]]},"references-count":23,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1002\/ajmg.a.36501"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36501","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,26]]}}}