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Lack of FAM20A, Ectopic Gingival Mineralization and Chondro/Osteogenic Modifications in Enamel Renal Syndrome
Enamel renal syndrome (ERS) is a rare recessive disorder caused by loss-of-function mutations in FAM20A (family with sequence similarity 20 member A, OMIM #611062). Enamel renal syndrome is characterized by amelogenesis imperfecta, delayed or failed tooth eruption, intrapulpal calcifications, gingiv...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793853/ https://www.ncbi.nlm.nih.gov/pubmed/33425910 http://dx.doi.org/10.3389/fcell.2020.605084 |
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author | Simancas Escorcia, Victor Diarra, Abdoulaziz Naveau, Adrien Dessombz, Arnaud Felizardo, Rufino Cannaya, Vidjeacoumary Chatziantoniou, Christos Quentric, Mickaël Vikkula, Miikka Cases, Olivier Berdal, Ariane De La Dure-Molla, Muriel Kozyraki, Renata |
author_facet | Simancas Escorcia, Victor Diarra, Abdoulaziz Naveau, Adrien Dessombz, Arnaud Felizardo, Rufino Cannaya, Vidjeacoumary Chatziantoniou, Christos Quentric, Mickaël Vikkula, Miikka Cases, Olivier Berdal, Ariane De La Dure-Molla, Muriel Kozyraki, Renata |
author_sort | Simancas Escorcia, Victor |
collection | PubMed |
description | Enamel renal syndrome (ERS) is a rare recessive disorder caused by loss-of-function mutations in FAM20A (family with sequence similarity 20 member A, OMIM #611062). Enamel renal syndrome is characterized by amelogenesis imperfecta, delayed or failed tooth eruption, intrapulpal calcifications, gingival overgrowth and nephrocalcinosis. Although gingival overgrowth has consistently been associated with heterotopic calcifications the pathogenesis, structure and interactions of the mineral deposits with the surrounding connective tissue are largely unknown. We here report a novel FAM20A mutation in exon 1 (c.358C > T) introducing a premature stop codon (p.Gln120*) and resulting in a complete loss of FAM20A. In addition to the typical oral findings and nephrocalcinosis, ectopic calcified nodules were also seen in the cervical and thoracic vertebrae regions. Histopathologic analysis of the gingiva showed an enlarged papillary layer associated with aberrant angiogenesis and a lamina propria displaying significant changes in its extracellular matrix composition, including disruption of the collagen I fiber network. Ectopic calcifications were found throughout the connective gingival tissue. Immunomorphological and ultrastructural analyses indicated that the calcification process was associated with epithelial degeneration and transformation of the gingival fibroblasts to chondro/osteoblastic-like cells. Mutant gingival fibroblasts cultures were prone to calcify and abnormally expressed osteoblastic markers such as RUNX2 or PERIOSTIN. Our findings expand the previously reported phenotypes and highlight some aspects of ERS pathogenesis. |
format | Online Article Text |
id | pubmed-7793853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77938532021-01-09 Lack of FAM20A, Ectopic Gingival Mineralization and Chondro/Osteogenic Modifications in Enamel Renal Syndrome Simancas Escorcia, Victor Diarra, Abdoulaziz Naveau, Adrien Dessombz, Arnaud Felizardo, Rufino Cannaya, Vidjeacoumary Chatziantoniou, Christos Quentric, Mickaël Vikkula, Miikka Cases, Olivier Berdal, Ariane De La Dure-Molla, Muriel Kozyraki, Renata Front Cell Dev Biol Cell and Developmental Biology Enamel renal syndrome (ERS) is a rare recessive disorder caused by loss-of-function mutations in FAM20A (family with sequence similarity 20 member A, OMIM #611062). Enamel renal syndrome is characterized by amelogenesis imperfecta, delayed or failed tooth eruption, intrapulpal calcifications, gingival overgrowth and nephrocalcinosis. Although gingival overgrowth has consistently been associated with heterotopic calcifications the pathogenesis, structure and interactions of the mineral deposits with the surrounding connective tissue are largely unknown. We here report a novel FAM20A mutation in exon 1 (c.358C > T) introducing a premature stop codon (p.Gln120*) and resulting in a complete loss of FAM20A. In addition to the typical oral findings and nephrocalcinosis, ectopic calcified nodules were also seen in the cervical and thoracic vertebrae regions. Histopathologic analysis of the gingiva showed an enlarged papillary layer associated with aberrant angiogenesis and a lamina propria displaying significant changes in its extracellular matrix composition, including disruption of the collagen I fiber network. Ectopic calcifications were found throughout the connective gingival tissue. Immunomorphological and ultrastructural analyses indicated that the calcification process was associated with epithelial degeneration and transformation of the gingival fibroblasts to chondro/osteoblastic-like cells. Mutant gingival fibroblasts cultures were prone to calcify and abnormally expressed osteoblastic markers such as RUNX2 or PERIOSTIN. Our findings expand the previously reported phenotypes and highlight some aspects of ERS pathogenesis. Frontiers Media S.A. 2020-12-08 /pmc/articles/PMC7793853/ /pubmed/33425910 http://dx.doi.org/10.3389/fcell.2020.605084 Text en Copyright © 2020 Simancas Escorcia, Diarra, Naveau, Dessombz, Felizardo, Cannaya, Chatziantoniou, Quentric, Vikkula, Cases, Berdal, De La Dure-Molla and Kozyraki. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Simancas Escorcia, Victor Diarra, Abdoulaziz Naveau, Adrien Dessombz, Arnaud Felizardo, Rufino Cannaya, Vidjeacoumary Chatziantoniou, Christos Quentric, Mickaël Vikkula, Miikka Cases, Olivier Berdal, Ariane De La Dure-Molla, Muriel Kozyraki, Renata Lack of FAM20A, Ectopic Gingival Mineralization and Chondro/Osteogenic Modifications in Enamel Renal Syndrome |
title | Lack of FAM20A, Ectopic Gingival Mineralization and Chondro/Osteogenic Modifications in Enamel Renal Syndrome |
title_full | Lack of FAM20A, Ectopic Gingival Mineralization and Chondro/Osteogenic Modifications in Enamel Renal Syndrome |
title_fullStr | Lack of FAM20A, Ectopic Gingival Mineralization and Chondro/Osteogenic Modifications in Enamel Renal Syndrome |
title_full_unstemmed | Lack of FAM20A, Ectopic Gingival Mineralization and Chondro/Osteogenic Modifications in Enamel Renal Syndrome |
title_short | Lack of FAM20A, Ectopic Gingival Mineralization and Chondro/Osteogenic Modifications in Enamel Renal Syndrome |
title_sort | lack of fam20a, ectopic gingival mineralization and chondro/osteogenic modifications in enamel renal syndrome |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793853/ https://www.ncbi.nlm.nih.gov/pubmed/33425910 http://dx.doi.org/10.3389/fcell.2020.605084 |
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