Novel ALPL genetic alteration associated with an odontohypophosphatasia phenotype

dc.creatorMartins, L
dc.creatorRodrigues, TL
dc.creatorRibeiro, MM
dc.creatorSaito, MT
dc.creatorGiorgetti, APO
dc.creatorCasati, MZ
dc.creatorSallum, EA
dc.creatorFoster, BL
dc.creatorSomerman, MJ
dc.creatorNociti, FH
dc.date2013
dc.dateOCT
dc.date2014-07-30T14:48:45Z
dc.date2015-11-26T17:41:17Z
dc.date2014-07-30T14:48:45Z
dc.date2015-11-26T17:41:17Z
dc.date.accessioned2018-03-29T00:23:04Z
dc.date.available2018-03-29T00:23:04Z
dc.identifierBone. Elsevier Science Inc, v. 56, n. 2, n. 390, n. 397, 2013.
dc.identifier8756-3282
dc.identifier1873-2763
dc.identifierWOS:000323864000023
dc.identifier10.1016/j.bone.2013.06.010
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/62134
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/62134
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1286968
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionHypopbosphatasia (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.
dc.description56
dc.description2
dc.description390
dc.description397
dc.descriptionIntramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionNational Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research (NIDCR) [DE15109]
dc.descriptionNIH [5R03TW007590-03]
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFAPESP [07/08192-5, 08/00534-7]
dc.descriptionCAPES [02426/09-9]
dc.descriptionCNPq [553386/200875]
dc.descriptionNational Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research (NIDCR) [DE15109]
dc.descriptionNIH [5R03TW007590-03]
dc.languageen
dc.publisherElsevier Science Inc
dc.publisherNew York
dc.publisherEUA
dc.relationBone
dc.relationBone
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectHypophosphatasia
dc.subjectOdontohypophosphatasia
dc.subjectTissue non-specific alkaline phosphatase
dc.subjectALPL
dc.subjectCollagen-binding site
dc.subjectCompound heterozygous mutations
dc.subjectNonspecific Alkaline-phosphatase
dc.subjectSwiss-model Workspace
dc.subjectProtein-structure
dc.subjectPerinatal Hypophosphatasia
dc.subjectLethal Hypophosphatasia
dc.subjectStructural Evidence
dc.subjectMissense Mutations
dc.subjectMineralization
dc.subjectDegradation
dc.subjectForms
dc.titleNovel ALPL genetic alteration associated with an odontohypophosphatasia phenotype
dc.typeArtículos de revistas


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