{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T03:52:29Z","timestamp":1782964349163,"version":"3.54.5"},"reference-count":28,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Genomics Thailand Research Grant of the Health Systems Research Institute (HSRI) of Thailand"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>One of the most important steps in post-translational modifications of collagen type I chains is the hydroxylation of carbon-3 of proline residues by prolyl-3-hydroxylase-1 (P3H1). Genetic variants in P3H1 have been reported to cause autosomal recessive osteogenesis imperfecta (OI) type VIII. Clinical and radiographic examinations, whole-exome sequencing (WES), and bioinformatic analysis were performed in 11 Thai children of Karen descent affected by multiple bone fractures. Clinical and radiographic findings in these patients fit OI type VIII. Phenotypic variability is evident. WES identified an intronic homozygous variant (chr1:43212857A &gt; G; NM_022356.4:c.2055 + 86A &gt; G) in P3H1 in all patients, with parents in each patient being heterozygous for the variant. This variant is predicted to generate a new \u201cCAG\u201d splice acceptor sequence, resulting in the incorporation of an extra exon that leads to a frameshift in the final exon and subsequent non-functional P3H1 isoform a. Alternative splicing of P3H1 resulting in the absence of functional P3H1 caused OI type VIII in 11 Thai children of Karen descent. This variant appears to be specific to the Karen population. Our study emphasizes the significance of considering intronic variants.<\/jats:p>","DOI":"10.3390\/genes14020322","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T01:58:59Z","timestamp":1674784739000},"page":"322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Founder Intronic Variant in P3H1 Likely Results in Aberrant Splicing and Protein Truncation in Patients of Karen Descent with Osteogenesis Imperfecta Type VIII"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9841-0881","authenticated-orcid":false,"given":"Piranit Nik","family":"Kantaputra","sequence":"first","affiliation":[{"name":"Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salita","family":"Angkurawaranon","sequence":"additional","affiliation":[{"name":"Division of Diagnostic Radiology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Worrachet","family":"Intachai","sequence":"additional","affiliation":[{"name":"Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chumpol","family":"Ngamphiw","sequence":"additional","affiliation":[{"name":"National Biobank of Thailand, National Science and Technology Development Agency, Khlong Luang, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sissades","family":"Tongsima","sequence":"additional","affiliation":[{"name":"National Biobank of Thailand, National Science and Technology Development Agency, Khlong Luang, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8015-5528","authenticated-orcid":false,"given":"Timothy C.","family":"Cox","sequence":"additional","affiliation":[{"name":"Departments of Oral & Craniofacial Sciences, School of Dentistry, and Pediatrics, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3042-1626","authenticated-orcid":false,"given":"James R.","family":"Ketudat Cairns","sequence":"additional","affiliation":[{"name":"Center for Biomolecular Structure, Function and Application and School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand"},{"name":"Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.4161\/cc.6.14.4474","article-title":"Components of the collagen prolyl 3-hydroxylation complex are crucial for normal bone development","volume":"6","author":"Marini","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_2","first-page":"975","article-title":"Distinct biochemical phenotypes predict clinical severity in nonlethal variants of osteogenesis imperfecta","volume":"46","author":"Wenstrup","year":"1990","journal-title":"Am. 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