Novel ALPL genetic alteration associated with an odontohypophosphatasia phenotype.

摘要: Hypophosphatasia (HPP) is an inherited disorder of mineral metabolism caused by mutations in ALPL, encoding tissue non-specific alkaline phosphatase (TNAP). Here, we report the molecular findings from monozygotic twins, clinically diagnosed with tooth-specific odontohypophosphatasia (odonto-HPP). Sequencing ALPL identified two genetic alterations probands, including a heterozygous missense mutation c.454C>T, leading to change arginine 152 cysteine (p.R152C), and novel gene deletion c.1318_1320delAAC, loss asparagine residue at codon 440 (p.N440del). Clinical identification low serum TNAP activity, dental abnormalities, pedigree data strongly suggests genotype-phenotype correlation between p.N440del odonto-HPP this family. Computational analysis protein structure revealed alteration tertiary affecting collagen-binding site (loop 422-452), which could potentially impair mineralization process. Nevertheless, probands (compound heterozygous: p.[N440del];[R152C]) feature early-onset severe phenotype, whereas father (p.[N440del];[=]) has only moderate symptoms, suggesting p.R152C may contribute or predispose more phenotype combination deletion. These results assist defining associations for odonto-HPP, further identify as region potential structural importance function biomineralization.