Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders

Tooth development is a complex process that involves precise and time-dependent orchestration of multiple genetic, molecular,and cellular interactions. Ameloblastin(AMBN, also named "amelin" or "sheathlin") is the second most abundant enamel matrix protein known to have a key role in amelogenesis. Amelogenesis imperfecta(AI [MIM: 104500]) refers to a genetically and phenotypically heterogeneous group of conditions characterized by inherited developmental enamel defects. The hereditary dentin disorders comprise a variety of autosomal-dominant genetic symptoms characterized by abnormal dentin structure affecting either the primary or both the primary and secondary teeth. The vital role of Ambn in amelogenesis has been confirmed experimentally using mouse models. Only two cases have been reported of mutations of AMBN associated with non-syndromic human AI. However, no AMBN missense mutations have been reported to be associated with both human AI and dentin disorders.We recruited one kindred with autosomal-dominant amelogenesis imperfecta(ADAI) and dentinogenesis imperfecta/dysplasia characterized by generalized severe enamel and dentin defects. Whole exome sequencing of the proband identified a novel heterozygous C-T point mutation at nucleotide position 1069 of the AMBN gene, causing a Pro to Ser mutation at the conserved amino acid position 357 of the protein. Exfoliated third molar teeth from the affected family members were found to have enamel and dentin of lower mineral density than control teeth, with thinner and easily fractured enamel, short and thick roots, and pulp obliteration. This study demonstrates, for the first time, that an AMBN missense mutation causes non-syndromic human AI and dentin disorders.

Esthetic and Functional Rehabilitation of Amelogenesis Imperfecta: Report of Four Cases with a One-Year Follow-Up

In this report, we describe the performance of a conservative and minimally invasive dental approach in four patients exhibiting Amelogenesis Imperfecta (AI), a structural anomaly of the enamel. In each patient, approximately 0.5 mm of the most external, porous, and colored enamel layer was removed, and the teeth were restored using two different nanocomposites. Posterior restorations were completed with the same approach. As a result, this contemporary restorative system is a conservative and successful treatment option to restore the loss of oral esthetics and function due to AI. Rehabilitation with direct resin restorations is not only an inexpensive treatment choice, but also a more conservative technique that reduces the amount of preparation required for teeth that are already compromised.

The rough-toothed dolphin genome provides new insights into the genetic mechanism of its rough teeth

The rough-toothed dolphin(Steno bredanensis)is characterized by having teeth covered infinely wrinkled vertical ridges,which is a general manifestation of amelogenesis imperfecta.The rough surfaces are hypothesized to be an evolutionary morphological trait of feeding adaptation to increase the dolphin’s grip on prey.Here,we assembled a rough-toothed dolphin genome and performed the comparative genomic analysis to reveal the genetic basis of the special enamel.Results showed that genes related to enamel development or dental diseases have undergone diver-sified adaptive changes that may shape the special enamel morphology of this dolphin species,including positive selection(CLDN19,PRKCE,SSUH2,and WDR72),rapid evolution(LAMB3),or unique amino acid substitutions(AMTN,ENAM,MMP20,and KLK4).Meanwhile,the historical demography of rough-toothed dolphin indicated several distinct populationfluctuations associated with climate change.The genome-wide heterozygosity of this dolphin is in the middle of all published data for cetaceans.Although the population is considerable,there may be population or subspecies differentiation,and with the global warming and the increasing disturbance of human activities,we should pay more attention to protection in the future.Together,our study brings new insights into the genetic mechanisms that may have driven the evolution of the special enamel morphology in rough-toothed dolphins and provides thefirst results of genetic heterozygosity and population historical dynamics of this species,which have important guiding implications for the conservation of this dolphin species.