Mutations in STARD8 (DLC3) May Cause 46,XY Gonadal Dysgenesis.

INTRODUCTION: 46,XY gonadal dysgenesis is a condition that is characterised by undeveloped testes in individuals with a male karyotype. Mutations in many genes that underlie this condition have been identified; however, there are still a considerable number of patients with an unknown genetic background. Recently, a mutation in the STARD8 X-linked gene in two sisters with 46,XY gonadal dysgenesis has been reported. It was localised within the START domain, whose homologue in Drosophila is responsible for maintaining testes integrity during their development. METHODS: We analysed the potential pathogenicity of another STARD8 mutation, p.R887C, that was identified in a patient with 46,XY asymmetric gonadal dysgenesis. For this purpose, molecular dynamics simulations were performed. RESULTS: These simulations revealed the full rearrangement of the helix containing the p.R887C substitution upstream from the START domain, which may cause STARD8 protein dysfunction and contribute to 46,XY gonadal dysgenesis. A comparison of the phenotypes of the three described 46,XY gonadal dysgenesis patients that harbour STARD8 mutations indicated that alterations of this gene can result in a partial or complete gonadal dysgenesis phenotype. CONCLUSION: Based on these and previous results, it is reasonable to include STARD8 in gene panels for 46,XY gonadal dysgenesis.

Relationship between hyperglycemia, waist circumference, and the course of COVID-19: Mortality risk assessment.

An observational study was conducted in Ukraine to determine the independent mortality risks among adult inpatients with COVID-19. The results of treatment of COVID-19 inpatients (n = 367) are presented, and waist circumference (WC) was measured. Logistic regression analysis was applied to evaluate the effects of factors on the risk of mortality. Odds ratios and 95% CIs for the association were calculated. One hundred and three of 367 subjects had fasting plasma glucose level that met the diabetes mellitus criteria (≥7.0 mmol/L), in 53 patients, diabetes mellitus was previously known. Two hundred and eleven patients did not have diabetes or hyperglycemia. Diabetes mellitus/hyperglycemia odds ratio 2.5 (CI 1.0-6.1), p = 0.045 loses statistical significance after standardization by age, waist circumference or fasting plasma glucose. No effect on gender, body mass index-determined obesity, or hypertension was found. The fasting plasma glucose (>8.5 mmol/L), age (≥61 years), and waist circumference (>105 cm) categories were associated with ORs 6.34 (CI 2.60-15.4); 4.12 (CI 1.37-12.4); 8.93 (CI 3.26-24.5), respectively. The optimal model of mortality risk with AUC 0.86 (CI 0.81-0.91) included the diabetes/heperglycemia and age categories as well as waist circumference as a continued variable. Waist circumference is an independent risk factor for mortality of inpatients with COVID-19.