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Clinical Orthopaedics and Related Research®

, Volume 468, Issue 2, pp 337–344 | Cite as

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

  • George Feldman
  • Chelsea Dalsey
  • Kasia Fertala
  • David Azimi
  • Paolo Fortina
  • Marcella Devoto
  • Maurizio Pacifici
  • Javad ParviziEmail author
Symposium: Papers Presented at the Hip Society Meetings 2009

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 α1, 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.

Keywords

Clubfoot Developmental Dysplasia Congenital Dislocation Extrusion Index Cheek Swab 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank Stephanie Barr, BS, for contributing to data collection; Javad Mortazavi, MD, Camilo Restrepo, MD, Orhan Bican, MD, and S. Mehdi Jafari, MD, for measuring radiographs for diagnostic purposes; and Charlene Williams, PhD, Kathryn Scott, BS, and Mark Bowser, BS, for contributing to data analysis.

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Copyright information

© The Association of Bone and Joint Surgeons® 2009

Authors and Affiliations

  • George Feldman
    • 1
  • Chelsea Dalsey
    • 1
  • Kasia Fertala
    • 1
  • David Azimi
    • 1
  • Paolo Fortina
    • 2
  • Marcella Devoto
    • 3
  • Maurizio Pacifici
    • 1
  • Javad Parvizi
    • 1
    Email author
  1. 1.Thomas Jefferson University and the Rothman Institute of OrthopaedicsPhiladelphiaUSA
  2. 2.Department of Cancer BiologyKimmel Cancer Center, Thomas Jefferson UniversityPhiladelphiaUSA
  3. 3.Division of Human GeneticsThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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