Odontohypophosphatasia caused by a novel combination of two heterozygous variants: a case report.

Hypophosphatasia (HPP) is a rare genetic disorder mainly characterized by skeletal dysplasia that results from a deficiency in tissue-nonspecific alkaline phosphatase (TNSALP), which is encoded by the alkaline phosphatase () gene. Odontohypophosphatasia (odonto-HPP) is a mild form of HPP characterized by oral symptoms, such as premature loss of primary teeth. This study was to describe a 4-year-old boy with premature loss of primary teeth who was diagnosed with odonto-HPP. X-ray radiography and laboratory examinations were performed for the diagnosis. Genetic etiology was revealed by whole-exome sequencing. A novel combination of two variants in the gene was identified in this case; this combination resulted in the odonto-HPP phenotype. c.346G>A (p.Ala116Thr) was inherited from the proband's father, whereas c.1563C>G (p.Ser521Arg) was inherited from the proband's mother. The proband's 8-year-old sister was a heterozygous carrier of c.346G>A (p.Ala116Thr) in the gene. Thus far, the proband's sister has been asymptomatic. Our findings indicate that c.346G>A is a pathogenic genetic alteration; c.1563C>G might cause a predisposition to the dental phenotype in combination with c.346G>A. It is important for pediatric dentists to consider a diagnosis of odonto-HPP in children with premature loss of primary teeth.