{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T19:05:42Z","timestamp":1784142342761,"version":"3.55.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Revitalizing Yunnan Talent Plan famous doctor","award":["XDYC-MY-2022-0094"],"award-info":[{"award-number":["XDYC-MY-2022-0094"]}]},{"name":"Revitalizing Yunnan Talent Plan famous doctor","award":["YNWR-MY-2020-066"],"award-info":[{"award-number":["YNWR-MY-2020-066"]}]},{"name":"Young and Middle-Aged Academic Leaders Planning Commission of Yunnan Province","award":["202105AC160034"],"award-info":[{"award-number":["202105AC160034"]}]},{"name":"Basic Research Project-Key Projects of Yunnan Province","award":["202301AS070007"],"award-info":[{"award-number":["202301AS070007"]}]},{"name":"Clinical Medical Center Open Project of the First People\u2019s Hospital of Yunnan Province","award":["2021LCZXXF-CS01"],"award-info":[{"award-number":["2021LCZXXF-CS01"]}]},{"name":"Open Project of Yunnan Provincial Key Laboratory for Research on Birth Defects and Genetic Diseases","award":["2022DKFKT004"],"award-info":[{"award-number":["2022DKFKT004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spondylometaphyseal dysplasia, Kozlowski type (SMDK), is an autosomal dominant skeletal disorder characterized by abnormalities of the spine, metaphyses and epiphyses. It is associated with variants in TRPV4, although the underlying molecular mechanisms remain unclear. A de novo heterozygous TRPV4 variant (c.2479C&amp;gt;G, p.Pro827Ala) was detected in a patient with SMDK by whole-exome sequencing, and transcriptome sequencing was performed in available family members. Expression analyses showed reduced TRPV4 transcript and protein levels associated with the p.Pro827Ala variant. Cellular functional assays further showed decreased intracellular Ca2+ concentrations without detectable changes in plasma membrane localization. In addition, ATP2B1 and PRKCQ were downregulated. To further investigate the pathogenic mechanism, a heterozygous knock-in Trpv4P827A\/+ mouse model was generated using CRISPR\/Cas9. Trpv4P827A\/P827A homozygous mice exhibited significant skeletal developmental delay, and transcriptome profiling revealed dysregulated expression of homeobox, zf_C2H2, and forkhead transcription factor families during early development. Collectively, these findings expand the spectrum of pathogenic TRPV4 variants and provide mechanistic insights into the pathogenic effect of TRPV4 p.Pro827Ala in SMDK, supporting improved clinical diagnosis and future functional studies.<\/jats:p>","DOI":"10.1093\/hmg\/ddag064","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:21:16Z","timestamp":1783336876000},"source":"Crossref","is-referenced-by-count":0,"title":["A\n                    <i>de novo TRPV4<\/i>\n                    variant c.2479C&amp;gt;G (p.Pro827Ala) in Spondylometaphyseal dysplasia Kozlowski type: identification and functional analysis"],"prefix":"10.1093","volume":"35","author":[{"given":"Congcong","family":"Teng","sequence":"first","affiliation":[{"name":"Medical School\/the First People\u2019s Hospital of Yunnan Province, Kunming University of Science and Technology , No.727 Jingming South Road, Chenggong District, Kunming 650500, Yunnan,","place":["China"]},{"name":"State 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Yunnan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhua","family":"Yang","sequence":"additional","affiliation":[{"name":"Medical College, Dali University , No.2 Hongsheng Road, Dali 671003, Yunnan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3283-8362","authenticated-orcid":false,"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Medical School\/the First People\u2019s Hospital of Yunnan Province, Kunming University of Science and Technology , No.727 Jingming South Road, Chenggong District, Kunming 650500, Yunnan,","place":["China"]},{"name":"Department of Medical Genetics, the First People\u2019s Hospital of Yunnan Province , No.157 Jinbi Road, Xishan District, Kunming 650032, Yunnan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuecheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, the First People\u2019s Hospital of Yunnan Province , No.157 Jinbi Road, Xishan District, Kunming 650032, Yunnan,","place":["China"]},{"name":"Department of Pediatrics, the Second Affiliated Hospital of Kunming Medical University , No.374 Dianmian Avenue, Wuhua District, Kunming 650101, Yunnan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Medical School\/the First People\u2019s Hospital of Yunnan Province, Kunming University of Science and Technology , No.727 Jingming South Road, Chenggong District, Kunming 650500, Yunnan,","place":["China"]},{"name":"Department of Medical Genetics, the First People\u2019s Hospital of Yunnan Province , No.157 Jinbi Road, Xishan District, Kunming 650032, Yunnan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Feng","sequence":"additional","affiliation":[{"name":"Medical School\/the First People\u2019s Hospital of Yunnan Province, Kunming University of Science and Technology , No.727 Jingming South Road, Chenggong District, Kunming 650500, Yunnan,","place":["China"]},{"name":"Department of Medical Genetics, the First People\u2019s Hospital of Yunnan Province , No.157 Jinbi Road, Xishan District, Kunming 650032, Yunnan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilun","family":"Cai","sequence":"additional","affiliation":[{"name":"Medical School\/the First People\u2019s Hospital of Yunnan Province, Kunming University of Science and Technology , No.727 Jingming South Road, Chenggong District, Kunming 650500, Yunnan,","place":["China"]},{"name":"Department of Medical Genetics, the First People\u2019s Hospital of Yunnan Province , No.157 Jinbi Road, Xishan District, Kunming 650032, Yunnan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxue","family":"Ni","sequence":"additional","affiliation":[{"name":"Medical School\/the First People\u2019s Hospital of Yunnan Province, Kunming University of Science and Technology , No.727 Jingming South Road, Chenggong District, Kunming 650500, Yunnan,","place":["China"]},{"name":"Department of Pediatrics, the First People\u2019s Hospital of Yunnan Province , No.157 Jinbi Road, Xishan District, Kunming 650032, Yunnan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0495-447X","authenticated-orcid":false,"given":"Hong","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology , No.727 Jingming South Road, Chenggong District, Kunming 650500, 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