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Genetics of Hypophosphatasia

  • Etienne Mornet
Original Paper

Abstract

Hypophosphatasia (HPP) results from mutations in the ALPL gene, mostly missense mutations. The gene is subject to a very high allelic heterogeneity, and some of these mutations have a dominant negative effect, two features that explain the most part of the clinical heterogeneity. Severe forms of the disease (perinatal and infantile) are inherited as an autosomal recessive trait. In the milder forms, autosomal recessive and autosomal dominant inheritance coexist. Experimental data show that there is a good correlation between the severity of the disease and in vitro alkaline phosphatase activity of the mutant protein. As a consequence of the existence of dominant mutations, moderate forms may be recessively or dominantly inherited and are expected more frequent than severe forms. The incidence of severe forms, inherited as a recessive trait, has been estimated at 1/300,000 in Europe. Genetic counseling is difficult in families where the mode of inheritance is unclear, or in prenatal context because of the prenatal benign form that may mimic severe perinatal HPP. During the ten last years, the mechanism of mineralization has been greatly deciphered, pointing out others gene that could modulate the HPP phenotype and explain particular cases where the phenotype does not correlate with the phenotype.

Keywords

Hypophosphatasia Genetics ALPL mutations Genotype–phenotype correlation Dominant inheritance 

Notes

Disclosures

Conflict of interest

Author Etienne Mornet declares that he has no conflict of interest.

Animal/Human Studies

This article does not contain any studies with human or animal subjects performed by the author.

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Unité de Pathologie cellulaire et génétiqueUPRES-EA2493, Université de Versailles Saint-Quentin en YvelinesVersaillesFrance
  2. 2.Unité de Génétique ConstitutionnelleCentre Hospitalier de VersaillesLe ChesnayFrance

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