| Autor: |
Fauvert Delphine, Brun-Heath Isabelle, Lia-Baldini Anne-Sophie, Bellazi Linda, Taillandier Agnès, Serre Jean-Louis, de Mazancourt Philippe, Mornet Etienne |
| Jazyk: |
angličtina |
| Rok vydání: |
2009 |
| Předmět: |
|
| Zdroj: |
BMC Medical Genetics, Vol 10, Iss 1, p 51 (2009) |
| Druh dokumentu: |
article |
| ISSN: |
1471-2350 |
| DOI: |
10.1186/1471-2350-10-51 |
| Popis: |
Abstract Background Mild hypophosphatasia (HPP) phenotype may result from ALPL gene mutations exhibiting residual alkaline phosphatase activity or from severe heterozygous mutations exhibiting a dominant negative effect. In order to determine the cause of our failure to detect a second mutation by sequencing in patients with mild HPP and carrying on a single heterozygous mutation, we tested the possible dominant effect of 35 mutations carried by these patients. Methods We tested the mutations by site-directed mutagenesis. We also genotyped 8 exonic and intronic ALPL gene polymorphisms in the patients and in a control group in order to detect the possible existence of a recurrent intronic mild mutation. Results We found that most of the tested mutations exhibit a dominant negative effect that may account for the mild HPP phenotype, and that for at least some of the patients, a second mutation in linkage disequilibrium with a particular haplotype could not be ruled out. Conclusion Mild HPP results in part from compound heterozygosity for severe and moderate mutations, but also in a large part from heterozygous mutations with a dominant negative effect. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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