{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T16:15:09Z","timestamp":1781540109174,"version":"3.54.5"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,5,29]],"date-time":"2013-05-29T00:00:00Z","timestamp":1369785600000},"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":[[2013,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Developmental dysplasia of the hip (DDH) is a debilitating condition characterized by incomplete formation of the acetabulum leading to dislocation of the femur, suboptimal joint function, and accelerated wear of the articular cartilage resulting in arthritis. DDH affects 1 in 1000 newborns in the United States; there are well-defined \u201cpockets\u201d of high prevalence in Japan, and in Italy and other Mediterranean countries. Although reasonably accurate for detecting gross forms of hip dysplasia, existing techniques fail to find milder forms of dysplasia. Undetected hip dysplasia is the leading cause of osteoarthritis of the hip in young individuals, causing over 40% of cases in this age group. A sensitive and specific test for DDH has remained a desirable yet elusive goal in orthopedics for a long time. A 72-member, four-generation affected family has been recruited, and DNA from its members retrieved. Genomewide linkage analysis revealed a 2.61-Mb candidate region (38.7\u201341.31 Mb from the p term of chromosome 3) co-inherited by all affected members with a maximum logarithm (base 10) of odds (LOD) score of 3.31. Whole exome sequencing and analysis of this candidate region in four severely affected family members revealed one shared variant, rs3732378, that causes a threonine (polar) to methionine (non-polar) alteration at position 280 in the transmembrane domain of CX3CR1. This mutation is predicted to have a deleterious effect on its encoded protein, which functions as a receptor for the ligand fractalkine. By Sanger sequencing this variant was found to be present in the DNA of all affected individuals and obligate heterozygotes. CX3CR1 mediates cellular adhesive and migratory functions and is known to be expressed in mesenchymal stem cells destined to become chondrocytes. A genetic risk factor that might be among the etiologic factors for the family in this study has been identified, along with other possible aggravating mutations shared by four severely affected family members. These findings might illuminate the molecular pathways affecting chondrocyte maturation and bone formation. \u00a9 2013 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.1999","type":"journal-article","created":{"date-parts":[[2013,5,29]],"date-time":"2013-05-29T10:57:10Z","timestamp":1369825030000},"page":"2540-2549","source":"Crossref","is-referenced-by-count":51,"title":["Developmental Dysplasia of the Hip: Linkage Mapping and Whole Exome Sequencing Identify a Shared Variant in <i>CX<\/i>\n                  <i>3<\/i>\n                  <i>CR<\/i>\n                  <i>1<\/i> in All Affected Members of a Large Multigeneration Family"],"prefix":"10.1093","volume":"28","author":[{"given":"George J","family":"Feldman","sequence":"first","affiliation":[{"name":"Division of Orthopaedic ResearchThomas Jefferson UniversityPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javad","family":"Parvizi","sequence":"additional","affiliation":[{"name":"Rothman Institute of OrthopaedicsPhiladelphiaPAUSA"},{"name":"Division of Orthopaedic ResearchThomas Jefferson UniversityPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Levenstien","sequence":"additional","affiliation":[{"name":"Division of GeneticsThe Children's Hospital of PhiladelphiaPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A","family":"Erickson","sequence":"additional","affiliation":[{"name":"University Orthopaedic CenterUniversity of UtahSalt Lake CityUTUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Fortina","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Devoto","sequence":"additional","affiliation":[{"name":"Department of Molecular MedicineUniversity of Rome \u201cLa Sapienza\u201dRomeItaly"},{"name":"Department of Biostatistics and Epidemiology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA"},{"name":"Department of Pediatrics, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA"},{"name":"Division of GeneticsThe Children's Hospital of PhiladelphiaPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L","family":"Peters","sequence":"additional","affiliation":[{"name":"University Orthopaedic CenterUniversity of UtahSalt Lake CityUTUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,5,29]]},"reference":[{"issue":"2","key":"2024020318330658000_jbmr1999-bib-0001","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/00016470510030517","article-title":"Hip dysplasia and osteoarthritis: a survey of 4,151 subjects from the Osteoarthrosis Substudy of the Copenhagen City Heart Study","volume":"76","author":"Jacobsen","year":"2005","journal-title":"Acta Orthop."},{"key":"2024020318330658000_jbmr1999-bib-0002","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s11999-008-0120-z","article-title":"Exclusion of COL2A1 and VDR as developmental dysplasia of the hip genes","volume":"466","author":"Rubini","year":"2008","journal-title":"Clin Orthop Relat Res."},{"key":"2024020318330658000_jbmr1999-bib-0003","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/j.1442-200X.2008.02575.x","article-title":"Developmental dysplasia of the hip: risk markers, clinical screening and outcome","volume":"50","author":"Stein-Zamir","year":"2008","journal-title":"Pediatr Int."},{"key":"2024020318330658000_jbmr1999-bib-0004","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/00003086-199208000-00013","article-title":"Etiologic factors in congenital displacement of the hip and myelodysplasia","volume":"281","author":"Wilkinson","year":"1992","journal-title":"Clin Orthop Relat Res."},{"key":"2024020318330658000_jbmr1999-bib-0005","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1097\/00003086-196801000-00020","article-title":"Congenital dysplasia of the hip in the Navajo infant","volume":"56","author":"Coleman","year":"1968","journal-title":"Clin Orthop."},{"issue":"4","key":"2024020318330658000_jbmr1999-bib-0006","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1302\/0301-620X.52B4.704","article-title":"Acetabular dysplasia and familial joint laxity: two etiological factors in congenital dislocation of the hip. 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