{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:25:36Z","timestamp":1762431936019,"version":"3.41.2"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/00153"],"award-info":[{"award-number":["PI17\/00153"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive tubulopathy characterized by excessive urinary wasting of magnesium and calcium, bilateral nephrocalcinosis, and progressive chronic renal failure in childhood or adolescence. FHHNC is caused by mutations in <jats:italic>CLDN16<\/jats:italic> and <jats:italic>CLDN19<\/jats:italic>, which encode the tight\u2010junction proteins claudin\u201016 and claudin\u201019, respectively. Most of these mutations are missense mutations and large deletions are rare.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined the clinical and biochemical features of a Spanish boy with early onset of FHHNC symptoms. Exons and flanking intronic segments of <jats:italic>CLDN16<\/jats:italic> and <jats:italic>CLDN19<\/jats:italic> were analyzed by direct sequencing. We developed a new assay based on Quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF) to investigate large <jats:italic>CLDN16<\/jats:italic> deletions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic analysis revealed two novel compound heterozygous mutations of <jats:italic>CLDN16<\/jats:italic>, comprising a missense mutation, c.277G&gt;A; p.(Ala93Thr), in one allele, and a gross deletion that lacked exons 4 and 5,c.(840+25_?)del, in the other allele. The patient inherited these variants from his mother and father, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Using direct sequencing and our QMPSF assay, we identified the genetic cause of FHHNC in our patient. This QMPSF assay should facilitate the genetic diagnosis of FHHNC. Our study provided additional data on the genotypic spectrum of the <jats:italic>CLDN16<\/jats:italic> gene.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1475","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T10:46:05Z","timestamp":1598957165000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel compound heterozygous mutations of <i>CLDN16<\/i> in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9734-6600","authenticated-orcid":false,"given":"Alejandro","family":"Garc\u00eda\u2010Casta\u00f1o","sequence":"first","affiliation":[{"name":"Biocruces Bizkaia Research Institute Barakaldo Bizkaia 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Investigaci\u00f3n Hospital Universitario Nuestra Se\u00f1ora de Candelaria Santa Cruz de Tenerife Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4032-9842","authenticated-orcid":false,"given":"Leire","family":"Madariaga","sequence":"additional","affiliation":[{"name":"Biocruces Bizkaia Research Institute Barakaldo Bizkaia Spain"},{"name":"Pediatric Nephrology Department Cruces University Hospital UPV\/EHU Barakaldo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1763-1098","authenticated-orcid":false,"given":"Gema","family":"Ariceta","sequence":"additional","affiliation":[{"name":"Fisiopatologia Renal Centro de Investigaciones en Bioqu\u00edmica y Biolog\u00eda Molecular (CIBBIM) Vall d\u2019Hebron Institut de Recerca (VHIR Barcelona Spain"},{"name":"Servicio de Nefrolog\u00eda Pedi\u00e1trica Hospital Universitari Vall d'Hebron Barcelona Spain"},{"name":"Departamento de 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