OBJECTIVE: To describe a large kinship with inherited hip osteoarthritis (OA) and its associated susceptibility locus. METHODS: Four generations of a kinship with familial hip OA were identified and characterized by family history and by clinical, radiographic, and histopathologic examination. In the genome-wide search for a susceptibility locus, OA cases were defined as those who had undergone total hip replacement associated with a clinical and radiographic diagnosis of hip OA. A genome-wide scan was performed using a framework set of microsatellite markers with an average spacing of 10 cM. RESULTS: The hip OA of this family was indistinguishable from that of idiopathic, nonfamilial hip OA. There was no apparent evidence of spondyloepiphyseal dysplasia or other dysplasias usually associated with mutations in collagen genes. The genome-wide scan revealed a locus on chromosome 16p between 28 cM and 47 cM from the telomere, and this locus met the criteria for suggestive linkage (multipoint allele-sharing logarithm of odds [LOD] score 2.58, P = 1.6 x 10(-4)). Two additional regions with LOD scores of >1.5 were obtained. CONCLUSION: We have identified and described the largest kinship with familial hip OA reported to date. Evidence for linkage in this family suggests that a gene for susceptibility to hip OA exists on chromosome 16p. This represents an independent identification of a susceptibility locus previously reported for hip OA in this geographic region.
OBJECTIVE: To describe a large kinship with inherited hip osteoarthritis (OA) and its associated susceptibility locus. METHODS: Four generations of a kinship with familial hip OA were identified and characterized by family history and by clinical, radiographic, and histopathologic examination. In the genome-wide search for a susceptibility locus, OA cases were defined as those who had undergone total hip replacement associated with a clinical and radiographic diagnosis of hip OA. A genome-wide scan was performed using a framework set of microsatellite markers with an average spacing of 10 cM. RESULTS: The hip OA of this family was indistinguishable from that of idiopathic, nonfamilial hip OA. There was no apparent evidence of spondyloepiphyseal dysplasia or other dysplasias usually associated with mutations in collagen genes. The genome-wide scan revealed a locus on chromosome 16p between 28 cM and 47 cM from the telomere, and this locus met the criteria for suggestive linkage (multipoint allele-sharing logarithm of odds [LOD] score 2.58, P = 1.6 x 10(-4)). Two additional regions with LOD scores of >1.5 were obtained. CONCLUSION: We have identified and described the largest kinship with familial hip OA reported to date. Evidence for linkage in this family suggests that a gene for susceptibility to hip OA exists on chromosome 16p. This represents an independent identification of a susceptibility locus previously reported for hip OA in this geographic region.
Authors: Unnur Styrkarsdottir; Hannes Helgason; Asgeir Sigurdsson; Gudmundur L Norddahl; Arna B Agustsdottir; Louise N Reynard; Amanda Villalvilla; Gisli H Halldorsson; Aslaug Jonasdottir; Audur Magnusdottir; Asmundur Oddson; Gerald Sulem; Florian Zink; Gardar Sveinbjornsson; Agnar Helgason; Hrefna S Johannsdottir; Anna Helgadottir; Hreinn Stefansson; Solveig Gretarsdottir; Thorunn Rafnar; Ina S Almdahl; Anne Brækhus; Tormod Fladby; Geir Selbæk; Farhad Hosseinpanah; Fereidoun Azizi; Jung Min Koh; Nelson L S Tang; Maryam S Daneshpour; Jose I Mayordomo; Corrine Welt; Peter S Braund; Nilesh J Samani; Lambertus A Kiemeney; L Stefan Lohmander; Claus Christiansen; Ole A Andreassen; Olafur Magnusson; Gisli Masson; Augustine Kong; Ingileif Jonsdottir; Daniel Gudbjartsson; Patrick Sulem; Helgi Jonsson; John Loughlin; Thorvaldur Ingvarsson; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2017-03-20 Impact factor: 38.330
Authors: C Greig; K Spreckley; R Aspinwall; E Gillaspy; M Grant; W Ollier; S John; M Doherty; G Wallis Journal: Ann Rheum Dis Date: 2006-02-27 Impact factor: 19.103
Authors: Hsiang-Cheng Chen; Virginia Byers Kraus; Yi-Ju Li; Sarah Nelson; Carol Haynes; Jessica Johnson; Thomas Stabler; Elizabeth R Hauser; Simon G Gregory; William E Kraus; Svati H Shah Journal: Arthritis Rheum Date: 2010-03