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Oro-dental phenotyping and report of three families with RELT-associated amelogenesis imperfecta

European Journal of Human Genetics volume 31, pages 1337–1341 (2023)Cite this article

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Abstract

Amelogenesis imperfecta (AI) is a group of rare genetic conditions characterized by quantitative and/or qualitative tooth enamel alterations. AI can manifest as an isolated trait or as part of a syndrome. Recently, five biallelic disease-causing variants in the RELT gene were identified in 7 families with autosomal recessive amelogenesis imperfecta (ARAI). RELT encodes an orphan receptor in the tumor necrosis factor (TNFR) superfamily expressed during tooth development, with unknown function. Here, we report one Brazilian and two French families with ARAI and a distinctive hypomineralized phenotype with hypoplastic enamel, post-eruptive enamel loss, and occlusal attrition. Using Next Generation Sequencing (NGS), four novel RELT variants were identified (c.120+1G>A, p.(?); c.120+1G>T, p.(?); c.193T>C, p.(Cys65Arg) and c.1260_1263dup, p.(Arg422Glyfs*5)). Our findings extend the knowledge of ARAI dental phenotypes and expand the disease-causing variants spectrum of the RELT gene.

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Fig. 1: Dental phenotype of three families with AI caused by homozygous or compound heterozygous RELT variants.

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Data availability

RELT variants were submitted to the Leiden Open Variation Database (LOVD).Variants IDs are 0000917717; 0000917923;0000917924;0000917925.

Code availability

The data generated and analyzed during this study can be found in the published article and its supplementary files.

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Acknowledgements

We thank Ms. Yorindel Cardozo for her assistance in the design of figure Appendix S6.

Funding

This study was supported by CAPES/COFECUB (Me918/2018) and the University of Brasilia (DPI/UnB, Brazil).

Author information

Author notes

  1. These authors contributed equally: Ana Carolina Acevedo, Muriel de La Dure-Molla.

Authors and Affiliations

  1. Laboratory of Oral Histopathology, Faculty of Health Sciences, University of Brasilia, Brasilia, Brazil

    Kemelly Karolliny Moreira Resende, Paulo Marcio Yamaguti & Ana Carolina Acevedo

  2. Oral Care Center for Inherited Diseases, University Hospital of Brasilia, Brasilia, Brazil

    Kemelly Karolliny Moreira Resende, Paulo Marcio Yamaguti & Ana Carolina Acevedo

  3. Reference Center of Oral and Dental Rare Diseases (O-Rares), Rothschild Hospital, Public Assistance- Paris Hospitals, Paris, France

    Margot Charlotte Riou, Benjamin Fournier, Ariane Berdal, Rufino Felizardo & Muriel de La Dure-Molla

  4. Paris Cité University, Dental Faculty, Paris, France

    Margot Charlotte Riou, Benjamin Fournier, Ariane Berdal, Rufino Felizardo, Ana Carolina Acevedo & Muriel de La Dure-Molla

  5. Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne University, UMRS 1138 Inserm, Molecular Oral Physiopathology, Paris, France

    Margot Charlotte Riou, Benjamin Fournier, Ariane Berdal & Ana Carolina Acevedo

  6. Reference Center for Skeletal Dysplasia, Service de Médecine Génomique des Maladies Rares, Necker Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

    Sophie Rondeau & Valérie Cormier-Daire

  7. Paris Cité University, INSERM UMR 1163 IMAGINE Institute, Paris, France

    Sophie Rondeau, Valérie Cormier-Daire & Muriel de La Dure-Molla

  8. Service de Médecine Génomique des Maladies de Système et d’Organe, Fédération de Génétique et de Médecine Génomique, APHP.Centre - Université Paris Cité, Hôpital Cochin, Paris, France

    Laurence Pacot & Céline Gaucher

  9. Institut Cochin, Inserm U1016, CNRS UMR8104, Université Paris Cité, CARPEM, Paris, France

    Laurence Pacot

  10. Laboratory of Clinical Genetics, Faculty of Medicine, University of Brasília, Brasília, Brazil

    Juliana Forte Mazzeu

  11. Université Paris Cité, URP2496, F-92120, Montrouge, France

    Céline Gaucher

  12. Department of Odontology, AP-HP, Hôpitaux Universitaire Henri Mondor, Paris, F-94000, France

    Céline Gaucher

Authors
  1. Kemelly Karolliny Moreira Resende
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  2. Margot Charlotte Riou
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  3. Paulo Marcio Yamaguti
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  4. Benjamin Fournier
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  5. Sophie Rondeau
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  6. Laurence Pacot
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  7. Ariane Berdal
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  8. Rufino Felizardo
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  9. Juliana Forte Mazzeu
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  10. Valérie Cormier-Daire
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  11. Céline Gaucher
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  12. Ana Carolina Acevedo
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  13. Muriel de La Dure-Molla
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Contributions

KKMR: Contributed to conception and design, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript. MCR: Contributed to conception and design, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript. PMY: Contributed to conception and design, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript. SR: Contributed to conception, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript. LP: Contributed to conception, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript. AB: Contributed to conception, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript. RF: Contributed to analysis, and interpretation, drafted and critically revised the manuscript. VC-D: Contributed to conception, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript. CG: Contributed to conception, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript. ACA: Contributed to conception and design, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript. MLD-M: Contributed to conception and design, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript. “All authors gave their final approval and agree to be accountable for all aspects of the work”.

Corresponding author

Correspondence to Muriel de La Dure-Molla.

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Competing interests

The authors declare no competing interests.

Ethical approval

This study was developed in compliance with the Declaration of Helsinki and approved by the Ethics Committee of the Health Sciences Faculty, University of Brasília and by the Ethics Committee from Rothschild Hospital. Informed consent for publication of individual details and images was signed by all legal guardians and/or patients that agreed to participate in the study.

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Resende, K.K.M., Riou, M.C., Yamaguti, P.M. et al. Oro-dental phenotyping and report of three families with RELT-associated amelogenesis imperfecta. Eur J Hum Genet 31, 1337–1341 (2023). https://doi.org/10.1038/s41431-023-01440-7

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  • DOI: https://doi.org/10.1038/s41431-023-01440-7

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