European Journal of Human Genetics - Clinical utility gene card for: Hypophosphatasia - update 2013

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European Journal of Human Genetics - Clinical utility gene card for: Hypophosphatasia - update 2013

Clinical Utility Gene Card Update

European Journal of Human Genetics advance online publication 7 August 2013; doi: 10.1038/ejhg.2013.177

Clinical utility gene card for: Hypophosphatasia – update 2013

Etienne Mornet^1,2, Christine Hofmann³, Agnès Bloch-Zupan^4,5,6, Hermann Girschick⁷ and Martine Le Merrer⁸

1. ¹Unité de Pathologie Cellulaire et Génétique UPRES-EA2493, Faculté de Médecine Paris Ile de France Ouest PRES Universud Paris, University of Versailles Saint Quentin en Yvelines, Versailles, France


2. ²Unité de Génétique Constitutionnelle, Centre Hospitalier de Versailles, Paris, France


3. ³Funktionsbereich Pädiatrische Rheumatologie, Immunologie und Osteologie, Kinderklinik und Poliklinik Universität Würzburg, Würzburg, Germany


4. ⁴Faculty of Dentistry, University of Strasbourg, Strasbourg, France


5. ⁵Reference Centre for Orodental Manifestations of Rare Diseases, Pôle de Médecine et Chirurgie Bucco-Dentaires, Hôpitaux Universitaires de Strasbourg, Strasbourg, France


6. ⁶Institute of Genetics and Molecular and Cellular Biology (IGBMC), Inserm U964, CNRS-UdS UMR7104, Illkirch, France


7. ⁷Vivantes Klinikum im Friedrichshain, Department of Pediatrics, Clinic for Pediatric and Adolescent Medicine, Berlin, Germany


8. ⁸U781 et Département de Génétique, Centre de Référence des Maladies Osseuses Constitutionnelles, Hopital Necker–Enfant Malades, Paris, France

Correspondence: Dr E Mornet, Unité de Génétique Constitutionnelle, Centre Hospitalier de Versailles, 2 rue Jean-Louis Forain, Le Chesnay 78150, France. Tel: +33 1 39 63 80 13; Fax: +33 1 39 63 80 12; E-mail: etienne.mornet@uvsq.fr

Update to: European Journal of Human Genetics (2010) 19, doi:10.1038/ejhg.2010.170; published online 27 October 2010

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1. DISEASE CHARACTERISTICS

1.1 Name of the disease (synonyms)

Hypophosphatasia (HP), HPP, rathbun disease and phosphoethanolaminuria.

1.2 OMIM# of the disease

146300, 241500 and 241510

1.3 Name of the analysed genes or DNA/chromosome segments

Alkaline phosphatase (AP) liver type (ALPL), 1p36.1-p34.

Used other names: TNAP and tissue nonspecific AP.

1.4 OMIM# of the gene(s)

171760.

1.5 Mutational spectrum

Over 250 different disease-causing mutations have been reported in the ALPL gene mutations.

Database http://www.sesep.uvsq.fr/03_hypo_mutations.php. The distribution is as follows: 75.5% missense mutations; 10.5% small deletions; 6% splicing mutations; 4% nonsense mutations; 2% small insertions; and 1% or less: complex insertion/deletions, large deletions and mutations in the regulatory sequence. The large proportion of missense mutations with various effects on the enzymatic activity of AP, based upon in vitro studies, has been correlated with the high clinical variability.¹ A number of missense mutations exhibit a dominant-negative effect^{2, 3, 4, 5} explaining dominant inheritance of mild forms of the disease.^{6, 7, 8}