title: Linkage mapping and whole exome sequencing identify a shared variant in CX3CR1 in a large multi-generation family.
abstract: Developmental dysplasia of the hip (DDH) is a crippling condition that affects children and adults, with an average incidence of 1-1.5 cases per 1000 live births. It results in disabling arthritis of the hip in up to 60% patients in the 20-40 year age group. There is no accurate diagnostic test available for newborns. The purpose of our study is to develop a sensitive and specific genetic test for DDH by identifying causative mutations. Linkage analysis and whole exome sequencing of 4 severely affected individuals of a 4 generation 71 member family was performed. The damaging rs3732378 variant in the CX3CR1 chemokine receptor was shared by all affected family members and by 15% of 28 sporadic dysplastics.
authors.affiliation: Thomas Jefferson University Division of Orthopaedic Research, Philadelphia, PA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Feldman
authors.affiliation: Thomas Jefferson University Division of Orthopaedic Research, Philadelphia, PA; Rothman Institute of Orthopaedics, Philadelphia, PA.
authors.forename: Javad
authors.initials: J
authors.lastname: Parvizi
authors.affiliation: Rothman Institute of Orthopaedics, Philadelphia, PA.
authors.forename: Hind
authors.initials: H
authors.lastname: Sawan
authors.affiliation: University Orthopaedic Center, University of Utah, Salt Lake City, UT.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Erickson
authors.affiliation: University Orthopaedic Center, University of Utah, Salt Lake City, UT.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Peters
mesh_terms: D000328:Adult; D000073883:CX3C Chemokine Receptor 1; D002648:Child; D002874:Chromosome Mapping; D059472:Exome; D005260:Female; D006618:Hip Dislocation, Congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D019707:Receptors, Chemokine / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014589:Utah
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D019707:Receptors, Chemokine
keywords: DNA variant; developmental dysplasia of the hip; linkage analysis; susceptibility inducing mutation; whole exome sequencing