{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:08:49Z","timestamp":1788419329276,"version":"build-2803163510"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"JSPS","doi-asserted-by":"publisher","award":["JP22K06848"],"award-info":[{"award-number":["JP22K06848"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"JSPS","doi-asserted-by":"publisher","award":["JP25K10158"],"award-info":[{"award-number":["JP25K10158"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Medical Research Council Clinician Scientist Award","award":["NMRC\/CSAINVJun21-0003"],"award-info":[{"award-number":["NMRC\/CSAINVJun21-0003"]}]},{"name":"National Medical Research Council Clinician Scientist Award","award":["NMRC\/CSAINV24jul-0001"],"award-info":[{"award-number":["NMRC\/CSAINV24jul-0001"]}]},{"name":"National Precision Medicine Programme","award":["MOH-000588"],"award-info":[{"award-number":["MOH-000588"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Transient neonatal hyperparathyroidism (TNHP) is a rare disorder characterized by severe skeletal abnormalities in newborns, resulting from insufficient maternal-fetal calcium transport across the placenta. Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) plays a significant role in placental calcium transport. While biallelic variants in the TRPV6 gene have been associated with TNHP, we present a case involving a neonate of Malay descent, born to non-consanguineous parents, who exhibited severe skeletal abnormalities at birth that resolved spontaneously within 6 wk. Biochemical evaluation revealed neonatal hyperparathyroidism alongside maternal vitamin D deficiency. Whole exome sequencing identified a novel paternally inherited heterozygous missense variant in the TRPV6 gene resulting in a valine-to-glutamic acid substitution at codon 625 (p.Val625Glu). This variant is situated adjacent to the TRP box, a region where a neighboring subunit is implicated in modulating channel gating via the S4-S5 linker. Functional studies were conducted by transfecting HEK293 cells with TRPV6-DsRed plasmids encoding either the wild-type or mutant protein. Immunocytochemistry demonstrated comparable cellular distribution between the variant and wild-type proteins. Western blot analysis confirmed the presence of both proteins at the plasma membrane. However, coimmunoprecipitation, intracellular calcium imaging, and patch-clamp studies suggested that the p.Val625Glu variant exerts a dominant-negative effect by interacting with the wild-type subunit to form a heteromeric complex, thereby impairing channel function. To our knowledge, this is the first report of a monoallelic TRPV6 variant associated with TNHP, expanding the understanding of its genetic underpinnings.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziaf159","type":"journal-article","created":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T11:37:07Z","timestamp":1760873827000},"source":"Crossref","is-referenced-by-count":2,"title":["Transient neonatal hyperparathyroidism caused by a monoallelic\n                    <i>TRPV6<\/i>\n                    dominant negative variant"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9849-7114","authenticated-orcid":false,"given":"Jason","family":"Lam Shang Leen","sequence":"first","affiliation":[{"name":"Department of Paediatrics, KK Women's and Children's Hospital , Singapore, 229899 ,","place":["Singapore"]},{"name":"Paediatric Academic Clinical Programme, Duke-NUS Medical School , Singapore, 169857 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-1867","authenticated-orcid":false,"given":"Yoshiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Physiology, Iwate Medical University , Iwate , 028-3694,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai Ling","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, KK Women's and Children's Hospital , Singapore, 229899 ,","place":["Singapore"]},{"name":"Paediatric Academic Clinical Programme, Duke-NUS Medical School , Singapore, 169857 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja Agarwal","family":"Jayagobi","sequence":"additional","affiliation":[{"name":"Paediatric Academic Clinical Programme, Duke-NUS Medical School , Singapore, 169857 ,","place":["Singapore"]},{"name":"Department of Neonatology, KK Women's and Children's Hospital , Singapore, 229899 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Radiology, Musashino-Yowakai Hospital , Tokyo , 180-0012,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4391-1130","authenticated-orcid":false,"given":"Weng Khong","family":"Lim","sequence":"additional","affiliation":[{"name":"SingHealth Duke-NUS Institute of Precision Medicine , SingHealth Duke-NUS Academic Centre, Singapore, 169609 ,","place":["Singapore"]},{"name":"SingHealth Duke-NUS Genomic Medicine Centre , SingHealth Duke-NUS Academic Centre, Singapore, 169609, Singapore"},{"name":"Cancer & Stem Cell Biology Program, Duke-NUS Medical School , Singapore, 169857,","place":["Singapore"]},{"name":"Genome Institute of Singapore, Agency for Science, Technology and Research , Singapore, 138672,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saumya Shekhar","family":"Jamuar","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, KK Women's and Children's Hospital , Singapore, 229899,","place":["Singapore"]},{"name":"Paediatric Academic Clinical Programme, Duke-NUS Medical School , Singapore, 169857,","place":["Singapore"]},{"name":"SingHealth Duke-NUS Institute of Precision Medicine , SingHealth Duke-NUS Academic Centre, Singapore, 169609,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashida Farhad","family":"Vasanwala","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, KK Women's and Children's Hospital , Singapore, 229899,","place":["Singapore"]},{"name":"Paediatric Academic Clinical Programme, Duke-NUS Medical School , Singapore, 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