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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RELT variants were submitted to the Leiden Open Variation Database (LOVD).Variants IDs are 0000917717; 0000917923;0000917924;0000917925.
The data generated and analyzed during this study can be found in the published article and its supplementary files.
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We thank Ms. Yorindel Cardozo for her assistance in the design of figure Appendix S6.
This study was supported by CAPES/COFECUB (Me918/2018) and the University of Brasilia (DPI/UnB, Brazil).
The authors declare no competing interests.
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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