Characterization of Missense Mutations and Large Deletions in theALPLGene by Sequencing and Quantitative Multiplex PCR of Short Fragments
- 1 January 2006
- journal article
- case report
- Published by Mary Ann Liebert Inc in Genetic Testing
- Vol. 10 (4), 252-257
- https://doi.org/10.1089/gte.2006.10.252
Abstract
Hypophosphatasia is a rare inherited bone disorder characterized by defective bone and dental mineralization and deficiency of serum and liver/bone/kidney alkaline phosphatase activity. The disease is due to mutations in the alkaline phosphatase liver-type (ALPL) gene. Gross deletions or insertions have not previously been reported in this gene. We report here the characterization of nine novel ALPL gene mutations in a series of 8 patients affected by various forms of hypophosphatasia. The newly discovered mutations included five missense mutations (c.368C → A, c.814C→ T, c.1196C→ T, c.1199C→ T, c.1283G→ C), two small deletions (c.797–802del, c.1044–1055del), and two large deletions. The large deletions were detected by quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments (QMPSF). We conclude that QMPSF slightly reduces the proportion of undetected mutations in hypophosphatasia and improves genetic counselling in the affected families.Keywords
This publication has 13 references indexed in Scilit:
- Molecular study of three cases of odontohypophosphatasia resulting from heterozygosity for mutations in the tissue non-specific alkaline phosphatase geneJournal of Medical Genetics, 2003
- PRODH mutations and hyperprolinemia in a subset of schizophrenic patientsHuman Molecular Genetics, 2002
- Rapid detection of novelBRCA1 rearrangements in high-risk breast-ovarian cancer families using multiplex PCR of short fluorescent fragmentsHuman Mutation, 2002
- Denaturing Gradient Gel Electrophoresis Analysis of the Tissue Nonspecific Alkaline Phosphatase Isoenzyme Gene in HypophosphatasiaMolecular Genetics and Metabolism, 2002
- Structural Evidence for a Functional Role of Human Tissue Nonspecific Alkaline Phosphatase in Bone MineralizationJournal of Biological Chemistry, 2001
- A molecular approach to dominance in hypophosphatasiaHuman Genetics, 2001
- Crystal Structure of Alkaline Phosphatase from Human Placenta at 1.8 Å ResolutionJournal of Biological Chemistry, 2001
- Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasiaEuropean Journal of Human Genetics, 1998
- Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralizationEndocrine Reviews, 1994
- Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia.Proceedings of the National Academy of Sciences of the United States of America, 1992