title: The Otto Aufranc Award: Identification of a 4 Mb region on chromosome 17q21 linked to developmental dysplasia of the hip in one 18-member, multigeneration family.
abstract: Developmental dysplasia of the hip (DDH) is a disabling condition that, depending on geography, can afflict between 20% and 80% of patients with end-stage arthritis of the hip. Despite its prevalence, the etiology of this disease remains unknown. DDH is a complex disorder with both environmental and genetic causes. Based on the literature the candidate genes for the disease are HOXB9, collagen type I alpha1, and DLX 3. The purpose of our study was to map and characterize the gene or genes responsible for this disorder by family linkage analysis. We recruited one 18-member, multigeneration affected family to provide cheek swabs and blood samples for isolation of DNA. Amplified DNA underwent a total genome scan using GeneChip Mapping 250 K Assay (Affymetrix, Santa Clara, CA). We observed only one region with a LOD score greater than 1.5: a 4 Mb region on chromosome 17q21.32, yielding a LOD score of 1.82. While a LOD score of 1.82 does not meet the accepted standard for linkage we interpret these data as suggesting the responsible gene could be linked to this region, which includes a cluster of homeobox genes (HOX genes) that are part of the developmental regulatory system providing cells with specific positional identities along the developing joint and spine. Discovering the genetic basis of the disease would be an important step in understanding the etiology of this disabling condition.
authors.affiliation: Thomas Jefferson University and the Rothman Institute of Orthopaedics, 925 Chestnut Street, 5th Floor, Philadelphia, PA 19107, USA.
authors.forename: George
authors.initials: G
authors.lastname: Feldman
authors.forename: Chelsea
authors.initials: C
authors.lastname: Dalsey
authors.forename: Kasia
authors.initials: K
authors.lastname: Fertala
authors.forename: David
authors.initials: D
authors.lastname: Azimi
authors.forename: Paolo
authors.initials: P
authors.lastname: Fortina
authors.forename: Marcella
authors.initials: M
authors.lastname: Devoto
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pacifici
authors.forename: Javad
authors.initials: J
authors.lastname: Parvizi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001363:Awards and Prizes; D002648:Child; D002886:Chromosomes, Human, Pair 17; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006618:Hip Dislocation, Congenital / Q000000981:diagnostic imaging / Q000235:genetics*; D006621:Hip Joint / Q000000981:diagnostic imaging; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D012307:Risk Factors; D012720:Severity of Illness Index