A novel dominant negative variant of <i>ALPL</i> induces hypophosphatasia.

ABSTRACT: Hypophosphatemia (HPP) is an inherited metabolic disorder characterized by defective bone and tooth mineralization, resulting from mutations in the gene encoding tissue-nonspecific alkaline phosphatase (ALPL). Despite the wide spectrum of clinical manifestations associated with ALPL mutations, the genotype-phenotype relationship remains poorly understood. In this work, we discovered a novel combination of missense mutations, p.G129E and p.Y263H. The patient with the mutations suffered from chronic musculoskeletal pain, arthralgia, and permanent dentition. Biochemical assays revealed that the Y263H mutation did not impair enzymatic function, but the G129E mutation significantly disrupted catalytic activity. Furthermore, G129E exhibited a dominant-negative effect by suppressing

SUBMITTER: Chen G 

PROVIDER: S-EPMC12448441 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature