Please use this identifier to cite or link to this item:
Type: Artigo de periódico
Title: Novel ALPL genetic alteration associated with an odontohypophosphatasia phenotype
Author: Martins, L
Rodrigues, TL
Ribeiro, MM
Saito, MT
Giorgetti, APO
Casati, MZ
Sallum, EA
Foster, BL
Somerman, MJ
Nociti, FH
Abstract: Hypopbosphatasia (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 of ALPL identified two genetic alterations in the probands, including a heterozygous missense mutation c.454C>T, leading to change of arginine 152 to cysteine (p.R152C), and a novel heterozygous gene deletion c.1318_1320delAAC, leading to the loss of an asparagine residue at codon 440 (p.N440de1). Clinical identification of low serum TNAP activity, dental abnormalities, and pedigree data strongly suggests a genotype-phenotype correlation between p.N440del and odonto-HPP in this family. Computational analysis of the p.N440del protein structure revealed an alteration in the tertiary structure affecting the collagen-binding site (loop 422-452), which could potentially impair the mineralization process. Nevertheless, the probands (compound heterozygous: p.[N440de1];[R152C]) feature early-onset and severe odonto-HPP phenotype, whereas the father (p.[N440del];[=]) has only moderate symptoms, suggesting p.R152C may contribute or predispose to a more severe dental phenotype in combination with the deletion. These results assist in defining the genotype-phenotype associations for odonto-HPP, and further identify the collagen-binding site as a region of potential structural importance for TNAP function in the biomineralization. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
Subject: Hypophosphatasia
Tissue non-specific alkaline phosphatase
Collagen-binding site
Compound heterozygous mutations
Country: EUA
Editor: Elsevier Science Inc
Citation: Bone. Elsevier Science Inc, v. 56, n. 2, n. 390, n. 397, 2013.
Rights: fechado
Identifier DOI: 10.1016/j.bone.2013.06.010
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.