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Novel mutation in the ALPL gene with a dominant negative effect in a Japanese family

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Title: Novel mutation in the ALPL gene with a dominant negative effect in a Japanese family
Authors: Kato, Masaru Browse this author →KAKEN DB
Michigami, Toshimi Browse this author
Tachikawa, Kanako Browse this author
Kato, Momoko Browse this author
Yabe, Ichiro Browse this author
Shimizu, Tomohiro Browse this author
Asaka, Takuya Browse this author
Kitagawa, Yoshimasa Browse this author
Atsumi, Tatsuya Browse this author
Keywords: Hypophosphatasia
Adult hypophosphatasia
ALPL gene
Novel mutation
Issue Date: 22-Oct-2021
Publisher: Springer
Journal Title: Journal of Bone and Mineral Metabolism
Volume: 39
Start Page: 804
End Page: 809
Publisher DOI: 10.1007/s00774-021-01219-0
Abstract: Introduction Hypophosphatasia (HPP) is caused by mutations in the ALPL gene encoding tissue nonspecific alkaline phosphatase (TNSALP) and inherited in either an autosomal recessive or autosomal dominant manner. It is characterized clinically by defective mineralization of bone, dental problems, and low serum ALP levels. In the current report, we demonstrate a novel mutation in the ALPL gene (c.244G > A p.Gly82Arg) in a Japanese family with low serum ALP levels. Materials and methods The ALPL gene analysis using hybridization capture-based next-generation sequencing was performed. The expression plasmids of the wild type and mutated TNSALP were introduced into COS-7 cells. The enzymatic activity of ALP in the cell lysates was measured using p-nitrophenylphosphate as a substrate. Results TNSALP with the novel ALPL mutation (c.244G > A p.Gly82Arg) completely lost its enzymatic activity and suppressed that of wild-type TNSALP, corroborating its dominant negative effect. The diagnosis of autosomal dominant HPP was confirmed in three members of the family. Conclusion Our approach would help to avoid the inappropriate use of bone resorption inhibitors for currently mis- or under-diagnosed HPP, given that the presence of further, yet undetected mutations of the ALPL gene are plausible.
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 加藤 将

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