{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:34:38Z","timestamp":1794004478878,"version":"4.8.0"},"reference-count":17,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T00:00:00Z","timestamp":1498176000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Orthod Craniofacial Res"],"published-print":{"date-parts":[[2017,6]]},"abstract":"Structured Abstract<\/jats:title>Objectives<\/jats:title>The genetic basis of PFE<\/jats:styled-content> (OMIM ID<\/jats:styled-content>: 125350) was interrogated using molecular functional studies. PFE<\/jats:styled-content> is a disorder that results in a poor prognosis in the eruption of teeth and by extension, in treatment with a continuous archwire. We tested the hypothesis that PTH<\/jats:styled-content>1R<\/jats:italic> mutations result in loss of function due to altered protein structure to determine (i) the fate of a functional PTH<\/jats:styled-content>1R<\/jats:italic> mutation and (ii) the resulting PTH<\/jats:styled-content>1R<\/jats:italic> protein structure of each functional mutation.<\/jats:p><\/jats:sec>Methods<\/jats:title>We used immunofluorescence assay of COS<\/jats:styled-content>7 cells that were transfected with either the WT<\/jats:styled-content> or 1092delG PTH<\/jats:styled-content>1R<\/jats:italic> mutation sequence to compare the fate of the expressed protein. We also performed in silico analysis of the WT <\/jats:styled-content>PTH<\/jats:styled-content>1R<\/jats:italic> and four different functional PTH<\/jats:styled-content>1R<\/jats:italic> mutations<\/jats:p><\/jats:sec>Results<\/jats:title>Functional studies (IFA<\/jats:styled-content>) showed a variation in expression between the WT<\/jats:styled-content> and mutant PTH<\/jats:styled-content>1R<\/jats:italic>. Further, in silico analysis showed structural differences between WT<\/jats:styled-content> and mutant PTH<\/jats:styled-content>1R proteins, particularly in the regions of the 3rd intracellular loop and the 6th transmembrane domain required for efficient PTH<\/jats:styled-content>1R function.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>PTH<\/jats:styled-content>1R<\/jats:italic> mutations identified in PFE<\/jats:styled-content> likely result from diminished function due to truncation of the protein, lack of efficient G\u2010protein interactions and putatively attenuated signal transduction. By identifying the mode of protein dysfunction, scientist\u2010clinicians are better prepared to recognize and thereby develop improved methods of treatment, starting at the molecular level.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ocr.12160","type":"journal-article","created":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T20:56:31Z","timestamp":1498251391000},"page":"57-62","source":"Crossref","is-referenced-by-count":14,"title":["In silico and functional evaluation of PTH<\/scp>1R<\/i> mutations found in patients with primary failure of eruption (PFE<\/scp>)"],"prefix":"10.1111","volume":"20","author":[{"given":"H. M.","family":"Hendricks","sequence":"first","affiliation":[{"name":"Department of Orthodontics The University of North Carolina at Chapel Hill Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Bencharit","sequence":"additional","affiliation":[{"name":"Departments of General Practice Oral & Maxillofacial Surgery, and Biomedical Engineering Virginia Commonwealth University Richmond VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Seaman","sequence":"additional","affiliation":[{"name":"The University of North Carolina at Chapel Hill Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. A.","family":"Frazier\u2010Bowers","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The University of North Carolina at Chapel Hill Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,23]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"Effective and Efficient Tooth Movement: Evidence Based Orthodontics","author":"Frazier\u2010Bowers SA","year":"2011"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9416(81)90217-7"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2013.03.015"},{"key":"e_1_2_6_5_1","volume-title":"Pediatric Bone: Biology & Diseases","author":"Glorieux FH","year":"2011"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.sodo.2010.05.003"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2009.10.021"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1067\/mod.2000.97938"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9416(62)90034-9"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-6343.2009.01440.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2006.09.038"},{"key":"e_1_2_6_12_1","first-page":"211","volume-title":"Molecular Aspects of G Protein\u2010Coupled Receptors: Interacting Proteins and Function","author":"Ciruela F","year":"2007"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2148-6-108"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.093138"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034513513588"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910508400407"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.11.2140"},{"key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1210\/mend.15.7.0665","article-title":"Analysis of parathyroid hormone (PTH)\/Secretin receptor chimeras differentiates the role functional domains in the PTH\/PTH\u2010Related peptide (PTHrP) receptor on hormone binding and receptor activation","volume":"15","author":"Vilargaga JP","year":"2001","journal-title":"Mol Endo"}],"container-title":["Orthodontics & Craniofacial Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Focr.12160","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ocr.12160","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T18:36:47Z","timestamp":1694630207000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ocr.12160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6]]},"references-count":17,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1111\/ocr.12160"],"URL":"https:\/\/doi.org\/10.1111\/ocr.12160","archive":["Portico"],"relation":{},"ISSN":["1601-6335","1601-6343"],"issn-type":[{"value":"1601-6335","type":"print"},{"value":"1601-6343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6]]}}}