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

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.