FAM20A Gene Mutation: Amelogenesis or Ectopic Mineralization?

Abstract

Background and objective: FAM20A gene mutations result in enamel renal syndrome (ERS) associated with amelogenesis imperfecta (AI), nephrocalcinosis, gingival fibromatosis, and impaired tooth eruption. FAM20A would control the phosphorylation of enamel peptides and thus enamel mineralization. Here, we characterized the structure and chemical composition of unerupted tooth enamel from ERS patients and healthy subjects.Methods: Tooth sections were analyzed by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-Ray Diffraction (XRD), and X-Ray Fluorescence (XRF).Results: SEM revealed that prisms were restricted to the inner-most enamel zones. The bulk of the mineralized matter covering the crown was formed by layers with varying electron-densities organized into lamellae and micronodules. Tissue porosity progressively increased at the periphery, ending with loose and unfused nanonodules also observed in the adjoining soft tissues. Thus, the enamel layer covering the dentin in all ERS patients (except a limited layer of enamel at the dentino-enamel junction) displayed an ultrastructural globular pattern similar to one observed in ectopic mineralization of soft tissue, notably in the gingiva of Fam20a knockout mice. XRD analysis confirmed the existence of alterations in crystallinity and composition (vs. sound enamel). XRF identified lower levels of calcium and phosphorus in ERS enamel. Finally, EDS confirmed the reduced amount of calcium in ERS enamel, which appeared similar to dentin.Conclusion: This study suggests that, after an initial normal start to amelogenesis, the bulk of the tissue covering coronal dentin would be formed by different mechanisms based on nano- to micro-nodule aggregation. This evocated ectopic mineralization process is known to intervene in several soft tissues in FAM20A gene mutant.

Enamel renal syndrome: A novel homozygous FAM20A founder mutation in 5 new Brazilian families

“…Furthermore, the patients were tested for alterations in their blood (calcium, ionized calcium, phosphate, parathyroid hormone, vitamin D (25OH and 1,25(OH)2), alkaline phosphatase and creatinine) and urine collected during 24 hours (calcium, phosphate, creatinine, osmolarity, specific gravity and glomerular filtration rate). Gingival tissues, teeth and pericoronary tissues removed for the purpose of oral rehabilitation were evaluated by classic H&E staining, and by screening electron microscopy (SEM) as published previously 17 .…”

Amelogenin phosphorylation regulates tooth enamel formation by stabilizing a transient amorphous mineral precursor

“…S2). Additional studies (81) have shown that erupted enamel from an ERS patient was mostly comprised of smaller and less organized enamel crystals, compared with normal enamel, which was reported to cover a thin "inner-most" layer of prismatic enamel adjacent to the DEJ. The enamel phenotypes observed in our S16A mutant mice that lack AMELX phosphorylation are quite similar to the reported enamel phenotypes in humans affected by mutations in a key kinase that is believed to play a critical role in amelogenesis.…”

Caracterización fenotípica del síndrome amelogénesis imperfecta–nefrocalcinosis: una revisión

“…Lignon et al 21 , utilizaron la microscopía electrónica de barrido (MEB) y métodos fisicoquímicos en pacientes con mutaciones FAM20A, constataron cristales pequeños y pocos compactados en todo el espesor del esmalte dental. La superficie del esmalte mostraba un patrón globular a nivel ultraestructural similar a la observada en la mineralización ectópica de tejidos blandos.…”

“…Análisis realizado por microscopia electrónica a transmisión revela que la talla de las mineralizaciones ectópicas gingivales es variable, en ocasiones únicas o fusionadas que pueden presentar un diámetro de 1 µm hasta 100µm. Esta característica sugiere que estas calcificaciones se fusionan con el tiempo 21 .…”

“…Según Ohyama et al 20, FAM20A es una pseudoquinasa que forma un complejo funcional con FAM20C y gracias a este complejo funcional, FAM20C incrementa 132 Caracterización fenotípica del síndrome amelogénesis imperfecta-nefrocalcinosis: una revisión DOI: http://dx.doi.org/10.21676/2389783X.2531 su capacidad de fosforilación. En consecuencia, las mutaciones del gen FAM20A contribuyen a una desregulación del microambiente celular del calcio y/o fosfato favoreciendo una alteración de los procesos regulatorios de la mineralización 21 .…”