Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation.

Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients.

Nephrocalcinosis (enamel renal syndrome) caused by autosomal recessive FAM20A mutations.

BACKGROUND/AIMS: Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood. METHODS: We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing. RESULTS: All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified. CONCLUSIONS: This autosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis.

Rehabilitation of an adolescent with autosomal dominant amelogenesis imperfecta: case report.

Amelogenesis imperfecta is a hereditary condition that affects tooth enamel without systemic involvement. In the most severely affected patients, teeth can present alterations in enamel thickness, color and shape, all which compromise aesthetic appearance and mastigatory function. Several treatment options have been described to rehabilitate these patients, ranging from preventive intervention to a prosthodontic approach. Advances in the search for new techniques and bonding materials have provided less invasive treatment options. This study discusses the importance of preventive procedures and describes the clinical procedures of aesthetic and functional rehabilitation of a Brazilian adolescent with autosomal dominant amelogenesis imperfecta (ADAI) involving the use of direct and indirect resin composite restorations.

Changes in amelogenesis in the rat incisor following short-term hypocalcaemia.

There is a relationship between hypocalcaemia and the enamel hypoplasia. Earlier studies in rats have reported a severe hypocalcaemia and enamel hypoplasia a month after thyro-parathyroidectomy (TPTX). The aims of this study were to look at earlier stages and to attempt to correlate morphological changes with alterations in the distribution of amelogenin. Twenty-five Wistar rats were, under anaesthesia, thyro-parathyroidectomized. Sham operated rats were included as controls. After 14, 30 or 57 days, the animals were reanesthatized and the tissues fixed by intracardiac perfusion of fixative. The lower incisors were processed for light microscopy and immunogold electron microscopy. After 14 days the thyro-parathyroidectomised rats were severely hypocalcaemic but amelogenesis was morphologically similar to controls. After 30 and 57 days, enamel defects were observed in the late secretory and early maturation stages in the thyro-parathyroidectomised rats. The immunocytochemical study revealed a concentration of stippled material immunolabelled for amelogenin at the secretory pole of the ameloblasts in the hypocalcaemic rats. The absence of enamel defects after 14 days suggests that this was an insufficient hypocalcaemic period to induce morphological alterations. The concentration of stippled material containing amelogenin suggests that alterations in matrix formation may be the basis of the morphological changes.