Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
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
_version_ 1783634081871822848
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
work_keys_str_mv AT simancasescorciavictor lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT diarraabdoulaziz lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT naveauadrien lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT dessombzarnaud lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT felizardorufino lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT cannayavidjeacoumary lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT chatziantoniouchristos lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT quentricmickael lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT vikkulamiikka lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT casesolivier lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT berdalariane lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT deladuremollamuriel lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome
AT kozyrakirenata lackoffam20aectopicgingivalmineralizationandchondroosteogenicmodificationsinenamelrenalsyndrome