Phenotype-genotype analysis of 242 individuals with RASopathies: 18-year experience of a tertiary center in Brazil.

We report the clinical and molecular data of a large cohort comprising 242 individuals with RASopathies, from a single Tertiary Center in Brazil, the largest study from Latin America. Noonan syndrome represented 76% of the subjects, with heterozygous variants in nine different genes, mainly PTPN11, SOS1, RAF1, LZTR1, and RIT1, detected by Sanger and next-generation sequencing. The latter was applied to 126 individuals, with a positive yield of 63% in genes of the RAS/MAPK cascade. We present evidence that there are some allelic differences in PTPN11 across distinct populations. We highlight the clinical aspects that pose more medical concerns, such as the cardiac anomalies, bleeding diathesis and proliferative lesions. The genotype-phenotype analysis between the RASopathies showed statistically significant differences in some cardinal features, such as craniofacial and cardiac anomalies, the latter also statistically significant for different genes in Noonan syndrome. We present two individuals with a Noonan syndrome phenotype, one with an atypical, structural cardiac defect, harboring variants in genes mainly associated with isolated hypertrophic cardiomyopathy and discuss the role of these variants in their phenotype.

Effect of mouth rinses with fluoride and trimetaphosphate on enamel erosion: an in vitro study.

The effect of mouth rinses containing fluoride (100 µg/ml) and sodium trimetaphosphate (TMP) on enamel erosion was evaluated in vitro. Bovine enamel blocks were subjected to erosive challenges 4 times per day for 5 min, followed by treatment with placebo, 225 µg F/ml, 100 µg F/ml, 100 µg F/ml and TMP (0.2, 0.4 and 0.6%) solutions (30 s) and storage in artificial saliva, over a duration of 5 days. TMP groups showed lower enamel wear than fluoride-only and placebo groups (p < 0.05). Addition of TMP at a TMP:NaF molar proportion between 1.24:1 and 3.72:1 to a solution containing 100 µg F/ml presented a greater protective effect under erosive conditions than a solution containing 225 µg F/ml, in the absence of TMP.