期刊
BMC MEDICAL GENETICS
卷 10, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-2350-10-51
关键词
-
资金
- Agence de la Biomedecine
- non-profit organization Hypophosphatasie Europe
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.
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