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  • Molecular study of three cases of odontohypophosphatasia resulting from heterozygosity for mutations in the tissue non-specific alkaline phosphatase gene

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Molecular study of three cases of odontohypophosphatasia resulting from heterozygosity for mutations in the tissue non-specific alkaline phosphatase gene
  1. M Herasse1,
  2. M Spentchian2,
  3. A Taillandier3,
  4. K Keppler-Noreuil4,
  5. A N M Fliorito5,
  6. J Bergoffen5,
  7. R Wallerstein6,
  8. C Muti3,
  9. B Simon-Bouy3,
  10. E Mornet1,3
  1. 1Laboratoire de Cytogénétique et Génétique Moléculaire Humaine, Université de Versailles Saint Quentin en Yvelines, Versailles, France
  2. 2Laboratoire de Biochimie, Centre Hospitalier de Versailles, Versailles, France
  3. 3Laboratoire SESEP, Université de Versailles-Saint Quentin en Yvelines, Versailles, France
  4. 4Division of Medical Genetics, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
  5. 5Kaiser Permanente Genetics Department, 5755 Cottle Road, Building 1, San Jose, CA 95123, USA
  6. 6Genetics Service, Hackensack University Medical Center, NJ 07601, USA
  1. Correspondence to:
 Dr E Mornet, Laboratoire de Cytogénétique et Génétique Moléculaire Humaine Batiment Fermat, Université de Versailles-Saint Quentin en Yvelines, 45 avenue des Etats-Unis, 78035 Versailles Cedex, France; 
 etienne.mornet{at}cytogene.uvsq.fr

https://doi.org/10.1136/jmg.40.8.605

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    Hypophosphatasia is an inherited disorder characterised by defective bone and tooth mineralisation and deficiency of serum and bone alkaline phosphatase activity. The bone symptoms are highly variable in their clinical expression and range from stillbirths without mineralised bone to pathological fractures developing only late in adulthood.1 Odontohypophosphatasia is characterised by premature exfoliation of fully rooted primary teeth and/or severe dental caries, often not associated with abnormalities of the skeletal system.2,3 The anterior deciduous teeth are more likely to be affected and the most frequently lost are the incisors.4 Dental x rays show reduced alveolar bone and enlarged pulp chambers and root canals.2,4 Although the only clinical feature is dental disease, biochemical findings are generally indistinguishable from those in patients with mild forms of hypophosphatasia (adult and childhood). While perinatal hypophosphatasia and infantile hypophosphatasia are transmitted as an autosomal recessive trait, both autosomal recessive and autosomal dominant transmission may be found in childhood, adult, and odontohypophosphatasia.3,5–9 The distinction between recessive and dominant transmission may be difficult to determine conclusively by using familial analysis because expression of the disease is very variable, with parents of even severely affected children showing no or extremely mild symptoms of the disease.9,10

    The tissue non-specific alkaline phosphatase (TNSALP) is a phosphomonoesterase anchored at its carboxyl terminus to the plasma membrane by a phosphatidylinositol-glycan moiety.11 The enzyme cleaves extracellular substrates pyridoxal-5′-phosphate (PLP), phosphoethanolamine (PEA), and inorganic pyrophosphates (PPi). Its exact function in bone and dental mineralisation is still unclear but probably involves hydrolysis of Ppi12 and perhaps mammalian specific activities such as collagen and calcium binding.13

    The TNSALP gene is localised on chromosome 1p36.114 and consists of 12 exons distributed over 50 kb.15 More than 127 distinct mutations have been described …

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