{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:26:00Z","timestamp":1790807160566,"version":"4.1.0"},"reference-count":22,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>Recessive forms of osteogenesis imperfecta (OI) may be caused by mutations in <jats:italic>LEPRE1<\/jats:italic>, encoding prolyl 3-hydroxylase-1 (P3H1) or in <jats:italic>CRTAP<\/jats:italic>, encoding cartilage associated protein. These proteins constitute together with cyclophilin B (CyPB) the prolyl 3-hydroxylation complex that hydroxylates the Pro986 residue in both the type I and type II collagen \u03b11-chains.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>We screened <jats:italic>LEPRE1<\/jats:italic>, <jats:italic>CRTAP<\/jats:italic> and <jats:italic>PPIB<\/jats:italic> (encoding CyPB) in a European\/Middle Eastern cohort of 20 lethal\/severe OI patients without a type I collagen mutation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Four novel homozygous and compound heterozygous mutations were identified in <jats:italic>LEPRE1<\/jats:italic> in four probands. Two probands survived the neonatal period, including one patient who is the eldest reported patient (17<jats:sup>7\/12<\/jats:sup> years) so far with P3H1 deficiency. At birth, clinical and radiologic features were hardly distinguishable from those in patients with autosomal dominant (AD) severe\/lethal OI. Follow-up data reveal that the longer lived patients develop a severe osteochondrodysplasia that overlaps with, but has some distinctive features from, AD OI. A new splice site mutation was identified in two of the four probands, affecting only one of three <jats:italic>LEPRE1<\/jats:italic> mRNA splice forms, detected in this study. The affected splice form encodes a 736 amino acid (AA) protein with a \u201cKDEL\u201d endoplasmic reticulum retention signal. While western blotting and immunocytochemical analysis of fibroblast cultures revealed absence of this P3H1 protein, mass spectrometry and SDS-urea-PAGE data showed severe reduction of \u03b11(I)Pro986 3-hydroxylation and overmodification of type I (pro)collagen chains in skin fibroblasts of the patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion:<\/jats:title>\n                  <jats:p>These findings suggest that the 3-hydroxylation function of P3H1 is restricted to the 736AA splice form.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2008.062729","type":"journal-article","created":{"date-parts":[[2008,12,16]],"date-time":"2008-12-16T22:38:21Z","timestamp":1229467101000},"page":"233-241","source":"Crossref","is-referenced-by-count":77,"title":["Recessive osteogenesis imperfecta caused by <i>LEPRE1<\/i> mutations: clinical documentation and identification of the splice form responsible for prolyl 3-hydroxylation"],"prefix":"10.1136","volume":"46","author":[{"given":"A","family":"Willaert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Malfait","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Symoens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Gevaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Kayserili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Megarbane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Mortier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J G","family":"Leroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P J","family":"Coucke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"De Paepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2008,12,16]]},"reference":[{"key":"2025101712512808000_46.4.233.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16051-0"},{"key":"2025101712512808000_46.4.233.2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1432-1033.1984.tb08114.x","article-title":"Formation of the triple helix of type I procollagen in cellulo. 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