Potential pathological role of single nucleotide polymorphism (c.787T > C) in alkaline phosphatase (ALPL) for the phenotypes of hypophosphatasia.

Potential pathological role of single nucleotide polymorphism (c.787T>C) in alkaline phosphatase (ALPL) for the phenotypes of hypophosphatasia. Endocr J. 2020 Aug 08;: Authors: Matsuda N, Takasawa K, Ohata Y, Takishima S, Kubota T, Ishihara Y, Fujiwara M, Ogawa E, Morio T, Kashimada K, Ozono K Abstract Hypophosphatasia (HPP; OMIM 241510, 241500, and 146300) is an inherited metabolic disease characterized by defects of bone and tooth mineralization, which is caused by loss-of-function mutations in the ALPL gene encoding tissue non-specific alkaline phosphatase (TNSALP). In the last three decades, several studies have focused on the genotype-phenotype correlation in hypophosphatasia (HPP). In particular, functional tests based on in vitro analysis for the residual enzymatic activities of mutations have revealed a clear but imperfect genotype-phenotype correlation, suggesting that multiple potential factors modulate the phenotype. One of the missense variants identified in the tissue non-specific alkaline phosphatase (ALPL) gene, c.787T>C, has been considered as a benign polymorphism in HPP; however, its pathogenicity and role in disease manifestation remain controversial. We here report our recent experience of three unrelated families harboring the c.787T>C variant, suggesting clinical implications regarding the controversial pathogenicity of c.787T>C. First, despite the lack of obvious clinical phenotypes, homozygous c.78...
Source: Endocrine Journal - Category: Endocrinology Tags: Endocr J Source Type: research