A Molecular-Based Estimation of the Prevalence of Hypophosphatasia in the European Population

Authors

  • Etienne Mornet,

    Corresponding author
    1. Unité de Pathologie Cellulaire et Génétique, UPRES-EA2493, Faculté de Médecine Paris Ile de France Ouest PRES Universud Paris, Université de Versailles-Saint Quentin en Yvelines, 78035 Versailles, France
    2. Laboratoire SESEP, Centre Hospitalier de Versailles, Le Chesnay, France
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  • Alice Yvard,

    1. Laboratoire SESEP, Centre Hospitalier de Versailles, Le Chesnay, France
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  • Agnes Taillandier,

    1. Laboratoire SESEP, Centre Hospitalier de Versailles, Le Chesnay, France
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  • Delphine Fauvert,

    1. Unité de Pathologie Cellulaire et Génétique, UPRES-EA2493, Faculté de Médecine Paris Ile de France Ouest PRES Universud Paris, Université de Versailles-Saint Quentin en Yvelines, 78035 Versailles, France
    2. Laboratoire SESEP, Centre Hospitalier de Versailles, Le Chesnay, France
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  • Brigitte Simon-Bouy

    1. Laboratoire SESEP, Centre Hospitalier de Versailles, Le Chesnay, France
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Corresponding author: Etienne Mornet, Laboratoire SESEP, Centre Hospitalier de Versailles, Bat EFS, 2 rue Jean-Louis Forain, 78150 Le Chesnay, France. Tel: 331 39 63 80 13; Fax: 331 39 63 80 12; E-mail: etienne.mornet@uvsq.fr

Summary

The prevalence of hypophosphatasia (HP), a rare metabolic disorder due to loss-of-function mutations in the ALPL gene, has never been estimated in the European population. Only one published study evaluated the incidence of severe HP at 1/100,000 in Canada 53 years ago. Moderate forms of hypophosphatasia (mHP), including HP with moderate bone features and the mildest form odontohypophosphatasia, reflect both recessive and dominant inheritance, and are therefore expected to be more frequent than severe forms of HP. Here we estimated both the prevalences of severe and mHP in European populations. The prevalence of severe HP was estimated at 1/300,000 on the basis of the number of cases tested in our laboratory and originating from France during the period 2000–2009. The prevalence of mHP was then estimated by using the proportion of dominant mutations among severe alleles and by estimating the penetrance of the disease in heterozygotes for dominant mutations. According to a genetic model with four alleles resulting in 10 distinct genotypes, the prevalence of dominant mHP in the European population was estimated to be 1/6370, pointing out that mHP is much more frequent than severe HP.

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