Background: The prevalence of Alport syndrome varies from one in 5,000 to one in 53,000. This study estimated the frequencies of predicted pathogenic COL4A3- COL4A5 variants in sequencing databases of populations without known kidney disease. Methods: Predicted pathogenic variants were identified using filtering steps based on the ACMG/AMP criteria that considered collagen IV α3-α5 position 1 Gly to be critical domains. The population frequencies of predicted pathogenic COL4A3-COL4A5 variants were then determined per mean number of sequenced alleles. Population frequencies for compound heterozygous and digenic combinations were calculated from the results for heterozygous variants. Results:COL4A3-COL4A5 variants resulting in position 1 Gly substitutions were confirmed associated with haematuria (p each <0.0001). Predicted pathogenic COL4A5 variants were found in at least one in 2,320 individuals. p.(Gly624Asp), represented nearly half (16/33, 48%) the variants in Europeans. Most COL4A5 variants (54/59, 92%) had a biochemical feature that potentially mitigated clinical impact. Predicted pathogenic heterozygous COL4A3 and COL4A4 variants affected one in 106 of the population, consistent with the finding of Thin basement membrane nephropathy in normal donor kidney biopsies. Predicted pathogenic compound heterozygous variants occurred in one in 88,866 individuals and digenic variants in at least one in 44,793. Conclusions: The population frequencies for Alport syndrome are suggested by the frequencies of predicted pathogenic COL4A3-COL4A5 variants but must be adjusted for the disease penetrance of individual variants, as well as the likelihood of already diagnosed disease and non-Gly substitutions. Disease penetrance may depend on other genetic and environmental factors.

A collection of intergenic suppressors of the Bacillus subtilis spoOF221 mutation has been isolated. One of these suppressors, rvtA, has been mapped between lys-1and aroD. The rvtA suppressor restores spoOF sporulation to wild type levels and substantially improves the sporulation efficiencies of spoOB and spoOE strains. The rvtA gene does not affect the Spo phenotype of spoOH, spoOJ or spoOK mutants. The rvtA gene also prevents the induction by aliphatic alcohols of SpoO phenocopies in wild type B. subtilis cells.

This study provides further evidence that the SAS is a simple and effective predictive tool in the emergency general and vascular surgical setting. It appears to have a limited role in the management of individual patients after orthopedic surgery and elective general/vascular surgery. The SAS has been proven to reliably stratify risk in larger populations and might be applied most usefully as a marker of quality. Further studies are required to determine whether its application can influence outcome.