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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

  • Symposium: Papers Presented at the Hip Society Meetings 2009
  • Published:
Clinical Orthopaedics and Related Research®

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.

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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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Authors and Affiliations

  1. Thomas Jefferson University and the Rothman Institute of Orthopaedics, 925 Chestnut Street, 5th Floor, Philadelphia, PA, 19107, USA

    George Feldman PhD, DMD, Chelsea Dalsey BA, Kasia Fertala BA, David Azimi BS, Maurizio Pacifici PhD & Javad Parvizi MD, FRCS

  2. Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Paolo Fortina MD

  3. Division of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Marcella Devoto PhD

Authors
  1. George Feldman PhD, DMD
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  2. Chelsea Dalsey BA
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  3. Kasia Fertala BA
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  4. David Azimi BS
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  5. Paolo Fortina MD
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  8. Javad Parvizi MD, FRCS
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Correspondence to Javad Parvizi MD, FRCS.

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Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.

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Feldman, G., Dalsey, C., Fertala, K. et al. 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. Clin Orthop Relat Res 468, 337–344 (2010). https://doi.org/10.1007/s11999-009-1073-6

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  • DOI: https://doi.org/10.1007/s11999-009-1073-6

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