Molecular and cellular basis of hypophosphatasia.
Alkaline phosphatase
Hypophosphatasia
Loss of function mutation
OMIM
Journal
Journal of oral biosciences
ISSN: 1880-3865
Titre abrégé: J Oral Biosci
Pays: Netherlands
ID NLM: 101226721
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
15
05
2019
revised:
10
07
2019
accepted:
11
07
2019
pubmed:
11
8
2019
medline:
28
3
2020
entrez:
11
8
2019
Statut:
ppublish
Résumé
Hypophosphatasia (HPP) is an inherited disorder characterized by defective mineralization of the bone and teeth that is also associated with a deficiency of serum alkaline phosphatase (ALP). Patients with HPP exhibit a broad range of symptoms including stillbirth with an unmineralized skeleton, premature exfoliation and dental caries in childhood, and pseudo-fractures in adulthood. The broad clinical spectrum of HPP is attributed to various mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). Nevertheless, the molecular mechanisms underlying the genotypic and phenotypic relationship of HPP remain unclear. The expression of HPP-related TNSALP mutants in mammalian cells allows us to determine for the effects of mutations on the properties of TNSALP, which could contribute to a better understanding of the relationship between structure and function of TNSALP. Molecular characterization of TNSALP mutants helps establish the etiology and onset of HPP.
Sections du résumé
BACKGROUND
Hypophosphatasia (HPP) is an inherited disorder characterized by defective mineralization of the bone and teeth that is also associated with a deficiency of serum alkaline phosphatase (ALP). Patients with HPP exhibit a broad range of symptoms including stillbirth with an unmineralized skeleton, premature exfoliation and dental caries in childhood, and pseudo-fractures in adulthood. The broad clinical spectrum of HPP is attributed to various mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). Nevertheless, the molecular mechanisms underlying the genotypic and phenotypic relationship of HPP remain unclear.
HIGHLIGHT
The expression of HPP-related TNSALP mutants in mammalian cells allows us to determine for the effects of mutations on the properties of TNSALP, which could contribute to a better understanding of the relationship between structure and function of TNSALP.
CONCLUSION
Molecular characterization of TNSALP mutants helps establish the etiology and onset of HPP.
Identifiants
pubmed: 31400546
pii: S1349-0079(19)30075-1
doi: 10.1016/j.job.2019.07.003
pii:
doi:
Substances chimiques
Alkaline Phosphatase
EC 3.1.3.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
141-148Informations de copyright
Copyright © 2019 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.