Novel ITGB6 Mutations Causing Amelogenesis Imperfecta

Background/Objectives: Amelogenesis imperfecta (AI) is a heterogeneous group of rare hereditary conditions mainly affecting the quantity and/or quality of tooth enamel. Its phenotypic expression is diverse, as is the mutational spectrum of the AI-causing genes and mutations. Integrins are cell-surface receptors that mediate adhesion between cells and between cells and the extracellular matrix. Among these, mutations in integrin αvβ6 have been shown to cause AI; however, phenotypic variation exists between the knockout mouse model and human cases, as well as among different human AI families. Methods: We recruited AI families and performed mutational analysis using whole exome sequencing. Results: We identified compound heterozygous ITGB6 mutations in two families. In Family 1, a paternally transmitted nonsense mutation (NM₀00888. 5: c. 1060C>T, p. (Gln354*) ) and a maternally transmitted missense mutation (NM₀00888. 5: c. 2312A>G, p. (Asn771Ser) ) were identified; in Family 2, a paternal missense mutation (NM₀00888. 5: c. 1693T>C, p. (Cys565Arg) ) and a maternal frameshift mutation (NM₀00888. 5: c. 2091delC, p. (Asn698Metfs*13) ) were identified, each causing AI in the respective proband. Both probands exhibited generalized hypoplastic and hypomineralized AI, but no other extraoral symptoms. Conclusions: This report will not only expand the known mutational spectrum of the ITGB6 gene but also provide evidence for the genotype–phenotype correlations, thereby improving our understanding of the functional role of ITGB6 during amelogenesis.