Mutations in RELT cause autosomal recessive amelogenesis imperfecta

Jung Wook Kim, Hong Zhang, Figen Seymen, Mine Koruyucu, Yuanyuan Hu, Jenny Kang, Youn J. Kim, Atsushi Ikeda, Yelda Kasimoglu, Merve Bayram, Chuhua Zhang, Kazuhiko Kawasaki, John D. Bartlett, Thomas L. Saunders, James P. Simmer, Jan C.C. Hu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)375-383
Number of pages9
JournalClinical Genetics
Volume95
Issue number3
DOIs
StatePublished - Mar 1 2019

Fingerprint

Amelogenesis Imperfecta
Dental Enamel
Mutation
Tumor Necrosis Factor Receptors
Incisor
Amelogenesis
Clustered Regularly Interspaced Short Palindromic Repeats
Dental Enamel Hypoplasia
Ameloblasts
Odontoblasts
RELT
Aptitude
Human Development
Genes
In Situ Hybridization
Tooth
History

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Kim, J. W., Zhang, H., Seymen, F., Koruyucu, M., Hu, Y., Kang, J., ... Hu, J. C. C. (2019). Mutations in RELT cause autosomal recessive amelogenesis imperfecta. Clinical Genetics, 95(3), 375-383. https://doi.org/10.1111/cge.13487
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. In: Clinical Genetics. 2019 ; Vol. 95, No. 3. pp. 375-383.
@article{16ba0bdb288544b8920e2f02d713e716,
title = "Mutations in RELT cause autosomal recessive amelogenesis imperfecta",
abstract = "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.",
author = "Kim, {Jung Wook} and Hong Zhang and Figen Seymen and Mine Koruyucu and Yuanyuan Hu and Jenny Kang and Kim, {Youn J.} and Atsushi Ikeda and Yelda Kasimoglu and Merve Bayram and Chuhua Zhang and Kazuhiko Kawasaki and Bartlett, {John D.} and Saunders, {Thomas L.} and Simmer, {James P.} and Hu, {Jan C.C.}",
year = "2019",
month = "3",
day = "1",
doi = "10.1111/cge.13487",
language = "English (US)",
volume = "95",
pages = "375--383",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",
number = "3",

}

Kim, JW, Zhang, H, Seymen, F, Koruyucu, M, Hu, Y, Kang, J, Kim, YJ, Ikeda, A, Kasimoglu, Y, Bayram, M, Zhang, C, Kawasaki, K, Bartlett, JD, Saunders, TL, Simmer, JP & Hu, JCC 2019, 'Mutations in RELT cause autosomal recessive amelogenesis imperfecta', Clinical Genetics, vol. 95, no. 3, pp. 375-383. https://doi.org/10.1111/cge.13487

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.

In: Clinical Genetics, Vol. 95, No. 3, 01.03.2019, p. 375-383.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mutations in RELT cause autosomal recessive amelogenesis imperfecta

AU - Kim, Jung Wook

AU - Zhang, Hong

AU - Seymen, Figen

AU - Koruyucu, Mine

AU - Hu, Yuanyuan

AU - Kang, Jenny

AU - Kim, Youn J.

AU - Ikeda, Atsushi

AU - Kasimoglu, Yelda

AU - Bayram, Merve

AU - Zhang, Chuhua

AU - Kawasaki, Kazuhiko

AU - Bartlett, John D.

AU - Saunders, Thomas L.

AU - Simmer, James P.

AU - Hu, Jan C.C.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85058947745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058947745&partnerID=8YFLogxK

U2 - 10.1111/cge.13487

DO - 10.1111/cge.13487

M3 - Article

C2 - 30506946

AN - SCOPUS:85058947745

VL - 95

SP - 375

EP - 383

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 3

ER -

Kim JW, Zhang H, Seymen F, Koruyucu M, Hu Y, Kang J et al. Mutations in RELT cause autosomal recessive amelogenesis imperfecta. Clinical Genetics. 2019 Mar 1;95(3):375-383. https://doi.org/10.1111/cge.13487