Hypophosphatasia now draws more attention of both clinicians and researchers: A Commentary on prevelance of c. 1559delT in ALPL, a common mutation resulting in the perinatal (lethal) form of hypophosphatasias in Japanese and effects of the mutation on heterozygous carriers

Ozono, Keiichi; Michigami, Toshimi

doi:10.1038/jhg.2011.6

Commentary
Published: 10 February 2011

Hypophosphatasia now draws more attention of both clinicians and researchers: A Commentary on prevelance of c. 1559delT in ALPL, a common mutation resulting in the perinatal (lethal) form of hypophosphatasias in Japanese and effects of the mutation on heterozygous carriers

Keiichi Ozono¹ &
Toshimi Michigami²

Journal of Human Genetics volume 56, pages 174–176 (2011)Cite this article

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Hypophosphatsia is a skeletal disease due to an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific alkaline phosphatase.^{1, 2} Alkaline phosphatase (ALP) is a membrane-bound metalloenzyme that consists of a group of isoenzymes encoded by four different gene loci: tissue-nonspecific, intestinal, placental and germ-cell ALP. Tissue-nonspecific alkaline phosphatase is expressed in almost all cells and three organs, liver, bone and kidney, have high activity of ALP. Thus, tissue-nonspecific alkaline phosphatase is also called ALP liver/bone/kidney (ALPL). The mouse counter part is called Akp2. Tissue-nonspecific alkaline phosphatase hydrolyzes inorganic pyrophosphate, an inhibitor of mineralization, and increases the local concentration of inorganic phosphate. Therefore, hypomineralization of skeleton and rachitic change of bone is associated with hypophosphatasia.

Hypophosphatasia is usually inherited in an autosomal recessive manner, but can be expressed in an autosomal dominant manner in milder forms.⁶ The ALPL gene is located on the short arm of chromosome 1 (1p36.1–p34), and contains 12 exons. The product consists of 507 amino acids including residues of the signal peptide. Hypophosphatasia is caused by various mutations in the ALPL gene. Currently, more than 200 mutations of the ALPL gene in patients with hypophosphatasia have been registered in the ALPL gene mutations database (http://www.sesep.uvsq.fr/Database.html). Most mutations described to date are missense mutations (80%), and the remainder was several deletion and insertion mutations of one to four nucleotides. Large deletions of the gene are rare (1.3%). Correlations of genotype and phenotype have been reported on the basis of clinical data of the patients with hypophosphatasia, enzymatic activity and computer-assisted modeling.²

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Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Keiichi Ozono
Department of Bone and Mineral Research Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan
Toshimi Michigami

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Ozono, K., Michigami, T. Hypophosphatasia now draws more attention of both clinicians and researchers: A Commentary on prevelance of c. 1559delT in ALPL, a common mutation resulting in the perinatal (lethal) form of hypophosphatasias in Japanese and effects of the mutation on heterozygous carriers. J Hum Genet 56, 174–176 (2011). https://doi.org/10.1038/jhg.2011.6

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Published: 10 February 2011
Issue date: March 2011
DOI: https://doi.org/10.1038/jhg.2011.6

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Hypophosphatasia now draws more attention of both clinicians and researchers: A Commentary on prevelance of c. 1559delT in ALPL, a common mutation resulting in the perinatal (lethal) form of hypophosphatasias in Japanese and effects of the mutation on heterozygous carriers

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Evaluation of alveolar bone hypomineralization in pediatric hypophosphatasia using orthopantomography

High-Level Expression of Alkaline Phosphatase by Adeno-Associated Virus Vector Ameliorates Pathological Bone Structure in a Hypophosphatasia Mouse Model

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