{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T22:21:52Z","timestamp":1768083712500,"version":"3.49.0"},"reference-count":33,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FE629\/2  WE4866\/1- 1 SFB894\/P2"],"award-info":[{"award-number":["FE629\/2  WE4866\/1- 1 SFB894\/P2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recently, we reported a case of an infant with neonatal severe under-mineralizing skeletal dysplasia caused by mutations within both alleles of the TRPV6 gene. One mutation results in an in frame stop codon (R510stop) that leads to a truncated, nonfunctional TRPV6 channel, and the second in a point mutation (G660R) that, surprisingly, does not affect the Ca2+ permeability of TRPV6. We mimicked the subunit composition of the unaffected heterozygous parent and child by coexpressing the TRPV6 G660R and R510stop mutants and combinations with wild type TRPV6. We show that both the G660R and R510stop mutant subunits are expressed and result in decreased calcium uptake, which is the result of the reduced abundancy of functional TRPV6 channels within the plasma membrane. We compared the proteomic profiles of a healthy placenta with that of the diseased infant and detected, exclusively in the latter two proteases, HTRA1 and cathepsin G. Our results implicate that the combination of the two mutant TRPV6 subunits, which are expressed in the placenta of the diseased child, is responsible for the decreased calcium uptake, which could explain the skeletal dysplasia. In addition, placental calcium deficiency also appears to be associated with an increase in the expression of proteases.<\/jats:p>","DOI":"10.3390\/ijms222312694","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T04:48:37Z","timestamp":1638247717000},"page":"12694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mutations That Affect the Surface Expression of TRPV6 Are Associated with the Upregulation of Serine Proteases in the Placenta of an Infant"],"prefix":"10.3390","volume":"22","author":[{"given":"Claudia","family":"Fecher-Trost","sequence":"first","affiliation":[{"name":"Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Buildings 61.4 and 46, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Wolske","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Buildings 61.4 and 46, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Wesely","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Buildings 61.4 and 46, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"L\u00f6hr","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Buildings 61.4 and 46, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel S.","family":"Klawitter","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Buildings 61.4 and 46, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3770-3749","authenticated-orcid":false,"given":"Petra","family":"Weissgerber","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Buildings 61.4 and 46, 66421 Homburg, Germany"},{"name":"Transgenic Technologies, Center for Molecular Signaling (PZMS), Saarland University, Building 61.4, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise","family":"Gradhand","sequence":"additional","affiliation":[{"name":"Kinder- und Perinatalpathologie Dr. Senckenberg, Institut f\u00fcr Pathologie Universit\u00e4tsklinikum Frankfurt\/Main Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine P.","family":"Burren","sequence":"additional","affiliation":[{"name":"Department of Translational Health Sciences, Bristol Medical School, University of Bristol, University Hospitals Bristol and Weston NHS Foundation Trust, Upper Maudlin St, Bristol BS2 8BJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7920-8186","authenticated-orcid":false,"given":"Anna E.","family":"Mason","sequence":"additional","affiliation":[{"name":"Histopathology Department, Aneurin Bevan University Health Board, Royal Gwent Hospital, Cardiff NP20 2UB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Winter","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Buildings 61.4 and 46, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Wissenbach","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Buildings 61.4 and 46, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19461","DOI":"10.1074\/jbc.M009895200","article-title":"Expression of CaT-like, a novel calcium-selective channel, correlates with the malignancy of prostate cancer","volume":"276","author":"Wissenbach","year":"2001","journal-title":"J. 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