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 au-tosomal 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.

The Amelogenesis Imperfecta (AI) are a group of clinically and genetically heterogeneous disorders that affect enamel formation. To date, mutations in 4 genes have been reported in various types of AI. Mutations in the genes encoding the 2 enamel proteases, matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4), have each been reported in a single family segregating autosomal-recessive hypomaturation AI. To determine the frequency of mutations in these genes, we analyzed 15 Turkish probands with autosomal-recessive hypomaturation AI for MMP20 and KLK4 gene mutations. No KLK4 mutations were found. A novel MMP20 mutation (g.16250T>A) was found in one family. This missense mutation changed the conserved active-site His226 residue of the zinc catalytic domain to Gln (p.H226Q). Zymogram analysis demonstrated that this missense mutation abolished MMP20 proteolytic activity. No MMP20 mutations were found in the remaining 14 probands, underscoring the genetic heterogeneity of hypomaturation AI.

Five mutations in the ENAM gene have been found to cause hypoplastic amelogenesis imperfecta (AI), with phenotypes ranging from localized enamel pitting in carriers to severe hypoplastic AI. To determine the generality of ENAM mutations in hypoplastic AI, we sequenced the ENAM gene in ten Turkish families segregating autosomal hypoplastic AI. In two families, ENAM mutations were found. A novel nonsense mutation (g.12663C>A; p.S246X) was identified in one family segregating local hypoplastic AI as a dominant trait. Affected individuals in a second family segregating autosomal-recessive AI were compound heterozygotes for a novel insertion mutation (g.12946_12947insAGTCAGTACCAGTACTGTGTC) and a previously described insertion (g.13185_13186insAG) mutation. Heterozygous carriers of either insertion had a localized enamel-pitting phenotype. These findings substantiate that enamel phenotypes of ENAM mutations may be dose-dependent, with generalized hypoplastic AI segregating as a recessive trait and localized enamel pitting segregating as a dominant trait.

Background: The aim of this study was to determine whether detectable periodontal destruction and alterations in the salivary status were present with duration of diabetes in children with type 1 insulin‐dependent diabetes mellitus (type 1 DM) as compared to healthy controls.Methods: Sixteen newly diagnosed children with DM (group 1), 16 children with type 1 DM of long duration (group 2), and 16 healthy children (group 3) participated in the study. Periodontal health was assessed by plaque index, gingival index, bleeding on probing, and periodontal probing depths. The flow rate, pH, buffering capacity, and peroxidase activities of stimulated saliva were determined. The data were analyzed by Kruskall‐Wallis, Student t test, and Pearson's correlation analysis.Results: The mean values for fasting blood glucose levels for the diabetic groups were significantly higher than for the controls. The mean values for salivary buffering capacities and salivary pH from the diabetic groups were significantly lower than for the controls. The plaque index values for the diabetic groups were significantly higher than for the controls. The mean gingival index value for group 1 was significantly lower than for group 2. The mean periodontal probing depths for group 1 were similar to those of the non‐DM controls, but the mean periodontal probing depths for group 2 were significantly greater than for both the non‐DM controls and group 1. Group 1 had significantly greater bleeding on probing scores than did the other groups (P <0.05).Conclusion: The glycemic status of the diabetic subjects affects the periodontal probing depths, salivary pH, buffering capacity, and peroxidase activity. J Periodontol 2003;74:1789‐1795.