{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:08:54Z","timestamp":1791857334787,"version":"4.3.4"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2011,3,14]],"date-time":"2011-03-14T00:00:00Z","timestamp":1300060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Massively parallel sequencing of target regions, exomes, and complete genomes has begun to increase the opportunities for identifying genetic variants underlying rare and common diseases dramatically. Here we applied exome resequencing to primary failure of tooth eruption (PFE) to identify the genetic causality of the disease. Two Japanese families having PFE were recruited and examined by genome-wide linkage study and subsequently exome analyses. Linkage analyses of these two families comprising eight affected individuals and two unaffected individuals revealed linkage signals at 10 loci with a maximum LOD score of 1.5. Four affected individuals in one family were pooled and further processed for exome analysis, followed by massive parallel sequencing. After three-step filtering including annotation and functional expectation, three variants were found to be candidates for PFE. Among the three variants, only a novel variant of parathyroid hormone 1 receptor gene (PTH1R), R383Q, was cosegregated in the first PFE family. Accordingly, we screened the gene for variants at all coding exons and the respective intron-exon boundaries in the second family and two sporadic individuals with PFE. We also identified a novel missense variant, P119L, cosegregating in the second family and missense variants P132L and R147C in the sporadic cases. These variants all were in the highly conserved region across zebrafish to chimpanzee and not observed in 192 unrelated controls, supporting the pathogenicity of the variants. The combination of linkage and exome analyses employed in this study provides a powerful strategy for identifying genes responsible for Mendelian disorders. \u00a9 2011 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.385","type":"journal-article","created":{"date-parts":[[2011,3,14]],"date-time":"2011-03-14T21:01:29Z","timestamp":1300136489000},"page":"1655-1661","source":"Crossref","is-referenced-by-count":57,"title":["Exome resequencing combined with linkage analysis identifies novel <i>PTH1R<\/i> variants in primary failure of tooth eruption in Japanese"],"prefix":"10.1093","volume":"26","author":[{"given":"Tetsutaro","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Hosomichi","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, National Institute of Genetics, Shizuoka, Japan"},{"name":"Department of Molecular Life Science, School of Medicine, Tokai University, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Narita","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Science, School of Medicine, Tokai University, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Shirota","sequence":"additional","affiliation":[{"name":"Department of Oral Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Tomoyasu","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koutaro","family":"Maki","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ituro","family":"Inoue","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, National Institute of Genetics, Shizuoka, Japan"},{"name":"Department of Molecular Life Science, School of Medicine, Tokai University, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,3,14]]},"reference":[{"key":"2024020318032138400_bib1","doi-asserted-by":"crossref","first-page":"19096","DOI":"10.1073\/pnas.0910672106","article-title":"Genetic diagnosis by whole exome capture and massively parallel DNA sequencing","volume":"106","author":"Choi","year":"2009","journal-title":"Proc Natl Acad Sci USA."},{"key":"2024020318032138400_bib2","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nature08250","article-title":"Targeted capture and massively parallel sequencing of 12 human exomes","volume":"461","author":"Ng","year":"2009","journal-title":"Nature."},{"key":"2024020318032138400_bib3","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/ng.499","article-title":"Exome sequencing identifies the cause of a mendelian disorder","volume":"42","author":"Ng","year":"2010","journal-title":"Nat Genet."},{"key":"2024020318032138400_bib4","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ajhg.2010.05.010","article-title":"Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82","volume":"87","author":"Walsh","year":"2010","journal-title":"Am J Hum Genet."},{"key":"2024020318032138400_bib5","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/ejo\/cjl033","article-title":"The clinical features and aetiological basis of primary eruption failure","volume":"28","author":"Ahmad","year":"2006","journal-title":"Eur J Orthod."},{"key":"2024020318032138400_bib6","first-page":"274","article-title":"Primary failure of eruption: a case report","volume":"41","author":"Pytlik","year":"1991","journal-title":"Int Dent J."},{"key":"2024020318032138400_bib7","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0002-9416(81)90217-7","article-title":"Primary failure of eruption: a possible cause of posterior open-bite","volume":"80","author":"Proffit","year":"1981","journal-title":"Am J Orthod."},{"key":"2024020318032138400_bib8","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ajodo.2003.10.031","article-title":"Delayed tooth eruption: pathogenesis, diagnosis, and treatment. 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