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Mutations in RELT cause autosomal recessive amelogenesis imperfecta

Amelogenesis imperfecta (AI) is a collection of isolated (non‐syndromic) inherited diseases affecting dental enamel formation or a clinical phenotype in syndromic conditions. We characterized three consanguineous AI families with generalized irregular hypoplastic enamel with rapid attrition that per...

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Autores principales: Kim, Jung‐Wook, Zhang, Hong, Seymen, Figen, Koruyucu, Mine, Hu, Yuanyuan, Kang, Jenny, Kim, Youn J., Ikeda, Atsushi, Kasimoglu, Yelda, Bayram, Merve, Zhang, Chuhua, Kawasaki, Kazuhiko, Bartlett, John D., Saunders, Thomas L., Simmer, James P., Hu, Jan C‐C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392136/
https://www.ncbi.nlm.nih.gov/pubmed/30506946
http://dx.doi.org/10.1111/cge.13487
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author Kim, Jung‐Wook
Zhang, Hong
Seymen, Figen
Koruyucu, Mine
Hu, Yuanyuan
Kang, Jenny
Kim, Youn J.
Ikeda, Atsushi
Kasimoglu, Yelda
Bayram, Merve
Zhang, Chuhua
Kawasaki, Kazuhiko
Bartlett, John D.
Saunders, Thomas L.
Simmer, James P.
Hu, Jan C‐C.
author_facet Kim, Jung‐Wook
Zhang, Hong
Seymen, Figen
Koruyucu, Mine
Hu, Yuanyuan
Kang, Jenny
Kim, Youn J.
Ikeda, Atsushi
Kasimoglu, Yelda
Bayram, Merve
Zhang, Chuhua
Kawasaki, Kazuhiko
Bartlett, John D.
Saunders, Thomas L.
Simmer, James P.
Hu, Jan C‐C.
author_sort Kim, Jung‐Wook
collection PubMed
description Amelogenesis imperfecta (AI) is a collection of isolated (non‐syndromic) inherited diseases affecting dental enamel formation or a clinical phenotype in syndromic conditions. We characterized three consanguineous AI families with generalized irregular hypoplastic enamel with rapid attrition that perfectly segregated with homozygous defects in a novel gene: RELT that is a member of the tumor necrosis factor receptor superfamily (TNFRSF). RNAscope in situ hybridization of wild‐type mouse molars and incisors showed specific Relt mRNA expression by secretory stage ameloblasts and by odontoblasts. Relt (−/−) mice generated by CRISPR/Cas9 exhibited incisor and molar enamel malformations. Relt (−/−) enamel had a rough surface and underwent rapid attrition. Normally unmineralized spaces in the deep enamel near the dentino‐enamel junction (DEJ) were as highly mineralized as the adjacent enamel, which likely altered the mechanical properties of the DEJ. Phylogenetic analyses showed the existence of selective pressure on RELT gene outside of tooth development, indicating that the human condition may be syndromic, which possibly explains the history of small stature and severe childhood infections in two of the probands. Knowing a TNFRSF member is critical during the secretory stage of enamel formation advances our understanding of amelogenesis and improves our ability to diagnose human conditions featuring enamel malformations.
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spelling pubmed-63921362019-03-07 Mutations in RELT cause autosomal recessive amelogenesis imperfecta Kim, Jung‐Wook Zhang, Hong Seymen, Figen Koruyucu, Mine Hu, Yuanyuan Kang, Jenny Kim, Youn J. Ikeda, Atsushi Kasimoglu, Yelda Bayram, Merve Zhang, Chuhua Kawasaki, Kazuhiko Bartlett, John D. Saunders, Thomas L. Simmer, James P. Hu, Jan C‐C. Clin Genet Original Articles Amelogenesis imperfecta (AI) is a collection of isolated (non‐syndromic) inherited diseases affecting dental enamel formation or a clinical phenotype in syndromic conditions. We characterized three consanguineous AI families with generalized irregular hypoplastic enamel with rapid attrition that perfectly segregated with homozygous defects in a novel gene: RELT that is a member of the tumor necrosis factor receptor superfamily (TNFRSF). RNAscope in situ hybridization of wild‐type mouse molars and incisors showed specific Relt mRNA expression by secretory stage ameloblasts and by odontoblasts. Relt (−/−) mice generated by CRISPR/Cas9 exhibited incisor and molar enamel malformations. Relt (−/−) enamel had a rough surface and underwent rapid attrition. Normally unmineralized spaces in the deep enamel near the dentino‐enamel junction (DEJ) were as highly mineralized as the adjacent enamel, which likely altered the mechanical properties of the DEJ. Phylogenetic analyses showed the existence of selective pressure on RELT gene outside of tooth development, indicating that the human condition may be syndromic, which possibly explains the history of small stature and severe childhood infections in two of the probands. Knowing a TNFRSF member is critical during the secretory stage of enamel formation advances our understanding of amelogenesis and improves our ability to diagnose human conditions featuring enamel malformations. Blackwell Publishing Ltd 2018-12-21 2019-03 /pmc/articles/PMC6392136/ /pubmed/30506946 http://dx.doi.org/10.1111/cge.13487 Text en © 2018 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Kim, Jung‐Wook
Zhang, Hong
Seymen, Figen
Koruyucu, Mine
Hu, Yuanyuan
Kang, Jenny
Kim, Youn J.
Ikeda, Atsushi
Kasimoglu, Yelda
Bayram, Merve
Zhang, Chuhua
Kawasaki, Kazuhiko
Bartlett, John D.
Saunders, Thomas L.
Simmer, James P.
Hu, Jan C‐C.
Mutations in RELT cause autosomal recessive amelogenesis imperfecta
title Mutations in RELT cause autosomal recessive amelogenesis imperfecta
title_full Mutations in RELT cause autosomal recessive amelogenesis imperfecta
title_fullStr Mutations in RELT cause autosomal recessive amelogenesis imperfecta
title_full_unstemmed Mutations in RELT cause autosomal recessive amelogenesis imperfecta
title_short Mutations in RELT cause autosomal recessive amelogenesis imperfecta
title_sort mutations in relt cause autosomal recessive amelogenesis imperfecta
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392136/
https://www.ncbi.nlm.nih.gov/pubmed/30506946
http://dx.doi.org/10.1111/cge.13487
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