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The genotype–phenotype correlation of hereditary multiple exostoses

Authors

  • C Alvarez,

    Corresponding author
    1. Department of Orthopaedics, Faculty of Medicine, University of British Columbia
    2. Department of Orthopaedics, British Columbia’s Children’s Hospital
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  • S Tredwell,

    1. Department of Orthopaedics, Faculty of Medicine, University of British Columbia
    2. Department of Orthopaedics, British Columbia’s Children’s Hospital
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  • M De Vera,

    1. Department of Orthopaedics, British Columbia’s Children’s Hospital
    2. Department of Health Care & Epidemiology
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  • M Hayden

    1. Department of Medical Genetics, University of British Columbia
    2. Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada
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Dr Christine Alvarez, Department of Orthopaedics, British Columbia’s Children’s Hospital, A203 – 4480 Oak Street, Vancouver, British Columbia, V6H 3V4 Canada
e-mail: calvarez@cw.bc.ca

Abstract

Hereditary multiple exostoses (HME) is an autosomal dominant condition with a wide spectrum of clinical presentations. The purpose of this study was to determine the relationship between the genotype and the phenotype in HME. Thirty-two affected individuals from 10 families participated in the study. An extensive description of HME phenotype in terms of the anatomical burden of disease involved clinical and radiographic examinations and evaluation of 76 parameters. Mutations were determined by sequencing the EXT 1 and EXT 2 genes. Mutations were found in eight families (26 individuals), with one mutation previously reported in the literature and seven novel mutations. There were seven subjects with an EXT 1 mutation and 16 with an EXT 2 mutation. Patients with EXT 1 mutation were found to have more exostoses, more limb malalignment with shorter limb segments and height, and more pelvic and flatbone involvement. A genotype–phenotype correlation exists in HME, with patients with EXT 1 mutations having a higher degree of anatomical burden.

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