Childhood hypophosphatasia due to a de novo missense mutation in the tissue-nonspecific alkaline phosphatase gene
- PMID: 15671102
- DOI: 10.1210/jc.2004-1456
Childhood hypophosphatasia due to a de novo missense mutation in the tissue-nonspecific alkaline phosphatase gene
Abstract
Hypophosphatasia is an inherited disorder due to mutations in the bone alkaline phosphatase (ALPL) gene. We report here a patient with childhood hypophosphatasia diagnosed at 1.4 yr because of pectus excavatum, large anterior fontanel, rachitic skeletal changes, and low serum alkaline phosphatase. Sequencing of the ALPL gene produced evidence of two distinct missense mutations, E174K (c.571G>A), of maternal origin, and a de novo mutation, M45I (c.186G>C). The study of various microsatellite polymorphisms ruled out false paternity and therefore confirmed that M45I occurred de novo in the paternal germline or in the early development of the patient. Site-directed mutagenesis showed that M45I results in the absence of in vitro alkaline phosphatase activity, suggesting that the mutation is a severe allele. In conclusion, childhood hypophosphatasia in this patient is the result of compound heterozygosity for the moderate mutation E174K and a novel severe de novo mutation M45I.
Similar articles
-
Evidence of a founder effect for the tissue-nonspecific alkaline phosphatase (TNSALP) gene E174K mutation in hypophosphatasia patients.Eur J Hum Genet. 2002 Oct;10(10):666-8. doi: 10.1038/sj.ejhg.5200857. Eur J Hum Genet. 2002. PMID: 12357339
-
Identification of the mutations in the tissue-nonspecific alkaline phosphatase gene in two Chinese families with hypophosphatasia.Arch Med Res. 2012 Jan;43(1):21-30. doi: 10.1016/j.arcmed.2012.01.004. Epub 2012 Jan 31. Arch Med Res. 2012. PMID: 22300680
-
Twelve novel mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL) in patients with various forms of hypophosphatasia.Hum Mutat. 2001;18(1):83-4. doi: 10.1002/humu.1154. Hum Mutat. 2001. PMID: 11438998
-
Hypophosphatasia: the mutations in the tissue-nonspecific alkaline phosphatase gene.Hum Mutat. 2000;15(4):309-15. doi: 10.1002/(SICI)1098-1004(200004)15:4<309::AID-HUMU2>3.0.CO;2-C. Hum Mutat. 2000. PMID: 10737975 Review.
-
First Korean Case of Infantile Hypophosphatasia with Novel Mutation in ALPL and Literature Review.Ann Clin Lab Sci. 2016 May;46(3):302-7. Ann Clin Lab Sci. 2016. PMID: 27312557 Review.
Cited by
-
Orodental phenotype and genotype findings in all subtypes of hypophosphatasia.Orphanet J Rare Dis. 2009 Feb 21;4:6. doi: 10.1186/1750-1172-4-6. Orphanet J Rare Dis. 2009. PMID: 19232125 Free PMC article.
-
Identification of altered brain metabolites associated with TNAP activity in a mouse model of hypophosphatasia using untargeted NMR-based metabolomics analysis.J Neurochem. 2017 Mar;140(6):919-940. doi: 10.1111/jnc.13950. J Neurochem. 2017. PMID: 28072448 Free PMC article.
-
Pyridoxine-Responsive Seizures in Infantile Hypophosphatasia and a Novel Homozygous Mutation in ALPL Gene.J Clin Res Pediatr Endocrinol. 2016 Sep 1;8(3):360-4. doi: 10.4274/jcrpe.2798. Epub 2016 Apr 18. J Clin Res Pediatr Endocrinol. 2016. PMID: 27086862 Free PMC article.
-
Hypophosphatasia: an overview of the disease and its treatment.Osteoporos Int. 2015 Dec;26(12):2743-57. doi: 10.1007/s00198-015-3272-1. Epub 2015 Aug 6. Osteoporos Int. 2015. PMID: 26245849 Review.
-
Case report: multiple fractures in a patient with mutations of TWIST1 and TNSALP.Clin Orthop Relat Res. 2008 Apr;466(4):990-6. doi: 10.1007/s11999-008-0123-9. Epub 2008 Jan 25. Clin Orthop Relat Res. 2008. PMID: 18219546 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous
