{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:16:34Z","timestamp":1789758994330,"version":"4.0.1"},"reference-count":24,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"published-print":{"date-parts":[[2011]]},"abstract":"<i>Background\/Aims:<\/i> Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare renal tubular disorder complicated by progressive renal failure during childhood or adolescence. Recently, causative mutations in the <i>CLDN19<\/i> gene have been identified in FHHNC patients presenting with severe ocular involvement. The aim of the study was to investigate the molecular genetic defect underlying FHHNC in a consanguineous Pakistani family. <i>Methods:<\/i> Clinical and biochemical parameters of the proband were studied during the follow-up period over 5 years. Genotyping of 7 members of the family was performed by amplifying microsatellite markers, tightly linked to the <i>CLDN16 <\/i>and <i>CLDN19<\/i> genes. The two genes were sequenced directly in an automated sequencer. PCR-RFLP assay and bioinformatic analysis were performed to verify the identified mutation. <i>Results:<\/i> Genotyping revealed that the proband was homozygous for the marker loci tightly linked to the <i>CLDN19<\/i> gene. Sequence analysis in the proband revealed homozygosity for a novel missense mutation in exon 3 of the <i>CLDN19<\/i> gene (389G>A) resulting in G130D amino acid substitution. Bioinformatic analysis supported the pathogenicity of the identified mutation. Family screening revealed nephrolithiasis in 3 of 6 (50%) heterozygous carriers of the pathogenic mutation. <i>Conclusion:<\/i> This study supports the fundamental role of claudin 19 for magnesium homeostasis, normal tubular structures in the kidney, and undisturbed organization and development of the retina.<\/jats:p>","DOI":"10.1159\/000330854","type":"journal-article","created":{"date-parts":[[2011,7,26]],"date-time":"2011-07-26T02:39:45Z","timestamp":1311647985000},"page":"241-248","source":"Crossref","is-referenced-by-count":39,"title":["Mutation in the Tight-Junction Gene Claudin 19 <i>(CLDN19)<\/i> and Familial Hypomagnesemia, Hypercalciuria, Nephrocalcinosis (FHHNC) and Severe Ocular Disease"],"prefix":"10.1159","volume":"34","author":[{"given":"Muhammad","family":"Naeem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naureen","family":"Akhtar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2011,7,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016%2F0026-0495%2872%2990025-X"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1152%2Fajprenal.00021.2004"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1007%2Fs00467-002-0884-4"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1210%2Fjc.2006-0200"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.ejhg.5200475"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1086%2F508617"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1006%2Fjmbi.2000.4042"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1101%2Fgr.176601"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016%2FS0168-9525%2800%2901988-0"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1093%2Fnar%2Fgkg115"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1136%2Fjmg.2005.033878"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016%2FS0076-6879%2896%2966034-0"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1034%2Fj.1600-0854.2001.020203.x"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.febslet.2006.01.019"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1371%2Fjournal.pgen.0010083"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1152%2Fphysiol.00034.2009"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1152%2Fajprenal.90264.2008"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1053%2Fj.ajkd.2010.08.038"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.2215%2FCJN.02870310"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.285.5424.103"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1242%2Fjcs.02631"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1523-1755.2000.00221.x"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1159%2F000045518"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1007%2Fs00467-006-0354-5"}],"container-title":["American Journal of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/330854","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/330854","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T14:33:34Z","timestamp":1745418814000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000330854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011]]},"references-count":24,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2011,9,1]]},"published-print":{"date-parts":[[2011,9,15]]}},"URL":"https:\/\/doi.org\/10.1159\/000330854","archive":["Portico"],"relation":{},"ISSN":["0250-8095","1421-9670"],"issn-type":[{"value":"0250-8095","type":"print"},{"value":"1421-9670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011]]}}}