Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia.

Details

Serval ID
serval:BIB_593FD3E90FD2
Type
Article: article from journal or magazin.
Collection
Publications
Title
Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia.
Journal
European Journal of Human Genetics
Author(s)
Mornet E., Taillandier A., Peyramaure S., Kaper F., Muller F., Brenner R., Bussière P., Freisinger P., Godard J., Le Merrer M., Oury J.F., Plauchu H., Puddu R., Rival J.M., Superti-Furga A., Touraine R.L., Serre J.L., Simon-Bouy B.
ISSN
1018-4813 (Print)
ISSN-L
1018-4813
Publication state
Published
Issued date
1998
Volume
6
Number
4
Pages
308-314
Language
english
Abstract
Hypophosphatasia is an inherited disorder characterised by defective bone mineralisation and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. We report the characterisation of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 13 European families affected by perinatal, infantile or childhood hypophosphatasia. Eighteen distinct mutations were found, only three of which had been reported previously in North American and Japanese populations. Most of the 15 new mutations were missense mutations, but we also found two mutations affecting donor splice sites and a nonsense mutation. A missense mutation in the last codon of the putative signal peptide probably affects the final maturation of the protein. Despite extensive sequencing of the gene and its promotor region, only one mutation was identified in two cases, one of which was compatible with a possible dominant effect of certain mutations and the putative role of polymorphisms of the TNSALP gene. In 12 of the 13 tested families, genetic diagnosis was possible by characterisation of the mutations or by use of polymorphisms as genetic markers. Hypophosphatasia diagnosis was assigned in two families where clinical, laboratory and radiographic data were unclear and prenatal diagnosis was performed in one case. The results also show that severe hypophosphatasia is due to a very large spectrum of mutations in European populations with no prevalent mutation and that genetic diagnosis of the disease must be performed by extensive analysis of the gene.
Keywords
Alkaline Phosphatase/genetics, Base Sequence, DNA Primers, Type="Geographic">Europe, Humans, Hypophosphatemia/diagnosis, Hypophosphatemia/enzymology, Mutation, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Prenatal Diagnosis
Pubmed
Open Access
Yes
Create date
14/03/2011 16:08
Last modification date
20/08/2019 14:12
Usage data