{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T19:40:53Z","timestamp":1772566853829,"version":"3.50.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1005003"],"award-info":[{"award-number":["2018YFC1005003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013145","name":"Primary Research and Development Plan of Zhejiang Province","doi-asserted-by":"publisher","award":["2021C03098"],"award-info":[{"award-number":["2021C03098"]}],"id":[{"id":"10.13039\/501100013145","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771535 81974224"],"award-info":[{"award-number":["81771535 81974224"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Osteogenesis imperfecta (OI) is a heterogeneous genetic disorder characterized by bone fragility. <jats:italic>PPIB<\/jats:italic> pathogenic variants cause a perinatal lethal form of OI type IX. A limited number of pathogenic variants have been reported so far worldwide.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We identified a rare pedigree whose phenotype was highly consistent with OI-IX. Exome sequencing was performed to uncover the causal variants. The variant pathogenicity was classified following the ACMG\/AMP guidelines. The founder effect and the age of the variant were assessed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We identified a homozygous missense variant c.509G &amp;gt; A\/p.G170D in <jats:italic>PPIB<\/jats:italic> in an affected fetus. This variant is a Chinese-specific allele and can now be classified as pathogenic. We estimated the allele frequency (AF) of this variant to be 0.0000427 in a Chinese cohort involving 128,781 individuals. All patients and carriers shared a common haplotype, indicative of a founder effect. The estimated age of variant was 65,160\u00a0years. We further identified pathogenic variants of <jats:italic>PPIB<\/jats:italic> in gnomAD and ClinVar databases, the conserved estimation of OI type IX incidence to be 1\/1,000,000 in Chinese population.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> We reported a founder pathogenic variant in <jats:italic>PPIB<\/jats:italic> specific to the Chinese population. We further provided our initial estimation of OI-IX disease incidence in China.<\/jats:p>","DOI":"10.3389\/fgene.2021.717294","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T06:18:44Z","timestamp":1632896324000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["A Founder Pathogenic Variant of PPIB Unique to Chinese Population Causes Osteogenesis Imperfecta IX"],"prefix":"10.3389","volume":"12","author":[{"given":"Wenting","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xijing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiqing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanna","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengpeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runju","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiping","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.ajhg.2010.02.022","article-title":"Mutations in the Gene Encoding the RER Protein FKBP65 Cause Autosomal-Recessive Osteogenesis Imperfecta","volume":"86","author":"Alanay","year":"2010","journal-title":"Am. 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