{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:29:59Z","timestamp":1792794599963,"version":"4.5.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T00:00:00Z","timestamp":1652400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["EJPRD2019-40"],"award-info":[{"award-number":["EJPRD2019-40"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IMAGEN"},{"DOI":"10.13039\/501100002997","name":"Dutch Kidney Foundation","doi-asserted-by":"publisher","award":["20OP+018"],"award-info":[{"award-number":["20OP+018"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["825575"],"award-info":[{"award-number":["825575"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Netherlands Organization for Scientific Research","award":["016.186.012"],"award-info":[{"award-number":["016.186.012"]}],"id":[{"id":"https:\/\/ror.org\/04jsz6e67","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Netherlands Organization for Scientific Research","award":["016.130.668"],"award-info":[{"award-number":["016.130.668"]}],"id":[{"id":"https:\/\/ror.org\/04jsz6e67","id-type":"ROR","asserted-by":"crossref"}]},{"name":"ISCIII-Subdirecci\u00f3n General de Evaluaci\u00f3n y Fomento de la Investigaci\u00f3n","award":["PI17\/00153"],"award-info":[{"award-number":["PI17\/00153"]}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypomagnesaemia with secondary hypocal-caemia (HSH) is a rare autosomal recessive disorder caused by pathogenic variants in TRPM6, encoding the channel-kinase transient receptor potential melastatin type 6. Patients have very low serum magnesium (Mg2+) levels and suffer from muscle cramps and seizures. Despite genetic testing, a subgroup of HSH patients remains without a diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, two families with an HSH phenotype but negative for TRPM6 pathogenic variants were subjected to whole exome sequencing. Using a complementary combination of biochemical and functional analyses in overexpression systems and patient-derived fibroblasts, the effect of the TRPM7-identified variants on Mg2+ transport was examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>For the first time, variants in TRPM7 were identified in two families as a potential cause for hereditary HSH. Patients suffer from seizures and muscle cramps due to magnesium deficiency and episodes of hypocalcaemia. In the first family, a splice site variant caused the incorporation of intron 1 sequences into the TRPM7 messenger RNA and generated a premature stop codon. As a consequence, patient-derived fibroblasts exhibit decreased cell growth. In the second family, a heterozygous missense variant in the pore domain resulted in decreased TRPM7 channel activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We establish TRPM7 as a prime candidate gene for autosomal dominant hypomagnesaemia and secondary hypocalcaemia. Screening of unresolved patients with hypocalcaemia and secondary hypocalcaemia may further establish TRPM7 pathogenic variants as a novel Mendelian disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfac182","type":"journal-article","created":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T08:29:43Z","timestamp":1652257783000},"page":"679-690","source":"Crossref","is-referenced-by-count":19,"title":["Possible role for rare\n                    <i>TRPM7<\/i>\n                    variants in patients with hypomagnesaemia with secondary hypocalcaemia"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4169-0680","authenticated-orcid":false,"given":"Rosa","family":"Vargas-Poussou","sequence":"first","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique, Centre de r\u00e9f\u00e9rence des Maladies R\u00e9nales H\u00e9r\u00e9ditaires de l'Enfant et de l'Adulte, H\u00f4pital Europ\u00e9en Georges Pompidou , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Claverie-Martin","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n, Renal Tube Group, Hospital Universitario Nuestra Se\u00f1ora de Candelaria , Santa Cruz de Tenerife , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Prot-Bertoye","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, INSERM, Universit\u00e9 de Paris, CNRS , Paris , France"},{"name":"Department of Physiology, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou , Paris , France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales H\u00e9r\u00e9ditaires de l'Enfant et de l'Adulte , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Carotti","sequence":"additional","affiliation":[{"name":"Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"van der Wijst","sequence":"additional","affiliation":[{"name":"Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Perdomo-Ramirez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n, Renal Tube Group, Hospital Universitario Nuestra Se\u00f1ora de Candelaria , Santa Cruz de Tenerife , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria M","family":"Fraga-Rodriguez","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Nefrolog\u00eda Pedi\u00e1trica, Hospital de la Santa Creu I Sant Pau , Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marguerite","family":"Hureaux","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique, Centre de r\u00e9f\u00e9rence des Maladies R\u00e9nales H\u00e9r\u00e9ditaires de l'Enfant et de l'Adulte, H\u00f4pital Europ\u00e9en Georges Pompidou , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5016-9435","authenticated-orcid":false,"given":"Caro","family":"Bos","sequence":"additional","affiliation":[{"name":"Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"Latta","sequence":"additional","affiliation":[{"name":"Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen , The 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2372-8486","authenticated-orcid":false,"given":"Jeroen H F","family":"de Baaij","sequence":"additional","affiliation":[{"name":"Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"key":"2023030115323853800_","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/ng889","article-title":"Hypomagnesaemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family","volume":"31","author":"Schlingmann","year":"2002","journal-title":"Nat Genet"},{"key":"2023030115323853800_","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/ng901","article-title":"Mutation of TRPM6 causes familial hypomagnesaemia with secondary 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