低磷性骨软化症的分子与细胞基础。

Molecular and cellular basis of hypophosphatasia.

作者信息

Komaru Keiichi, Ishida-Okumura Yoko, Numa-Kinjoh Natsuko, Hasegawa Tomoka, Oda Kimimitsu

机构信息

Kitasato Junior College of Health and Hygienic Science, 500 Kurotsuchi-Shinden, Minami-Uonoma, Niigata 949-7241, Japan.

Niigata University Graduate School of Medical and Dental Sciences 2-5274, Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.

出版信息

J Oral Biosci. 2019 Sep;61(3):141-148. doi: 10.1016/j.job.2019.07.003. Epub 2019 Aug 8.

DOI:10.1016/j.job.2019.07.003

PMID:31400546

Abstract

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.

摘要

背景

低磷性骨软化症（HPP）是一种遗传性疾病，其特征为骨骼和牙齿矿化缺陷，还与血清碱性磷酸酶（ALP）缺乏有关。HPP患者表现出广泛的症状，包括死产且骨骼未矿化、儿童期过早牙齿脱落和龋齿，以及成年期假性骨折。HPP广泛的临床谱归因于ALPL基因中的各种突变，该基因编码组织非特异性碱性磷酸酶（TNSALP）。然而，HPP基因型和表型关系背后的分子机制仍不清楚。