RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1

Despite being the first homolog of the bacterial RecQ helicase to be identified in humans, the function of RECQL1 remains poorly characterized. Furthermore, unlike other members of the human RECQ family of helicases, mutations in RECQL1 have not been associated with a genetic disease. Here, we identify 2 families with a genome instability disorder that we have named RECON (RECql ONe) syndrome, caused by biallelic mutations in the RECQL gene. The affected individuals had short stature, progeroid facial features, a hypoplastic nose, xeroderma, and skin photosensitivity and were homozygous for the same missense mutation in RECQL1 (p.Ala459Ser), located within its zinc binding domain. Biochemical analysis of the mutant RECQL1 protein revealed that the p.A459S missense mutation compromised its ATPase, helicase, and fork restoration activity, while its capacity to promote single-strand DNA annealing was largely unaffected. At the cellular level, this mutation in RECQL1 gave rise to a defect in the ability to repair DNA damage induced by exposure to topoisomerase poisons and a failure of DNA replication to progress efficiently in the presence of abortive topoisomerase lesions. Taken together, RECQL1 is the fourth member of the RecQ family of helicases to be associated with a human genome instability disorder.     

The Impact of COVID-19 Lockdown on the Incidence of Type 1 DM and the Glycemic Control of Diabetic Children: Findings from a Teaching Hospital,Saudi Arabia

OBJECTIVEWe evaluated glycemic control among T1DM pediatric patients attending the endocrinology pediatrics clinics at King Fahd Hospital of the University (KFHU) prior to and during COVID-19 restraining regulations. In addition, we assessed the trends and variations in the incidence of T1DM during 2017-2021, including the COVID-19 years by identifying newly diagnosed patients presenting to pediatrics emergency department (ED) in KFHU.METHODSTo estimate the effect of COVID-19 on the incidence of T1DM, we identified newly diagnosed cases of T1DM among pediatric patients attending the ED during the years 20172021. The participants’ data were collected through electronic medical records. Information collected included patient age, sex, and HbA1c readings. Three HbA1c readings of interest that were defined and collected are pre-COVID reading, in-COVID reading, and post-COVID reading.RESULTSThe difference of female participants’ readings was statistically non-significant (Z= -0.416, p = 0.678), with a pre- and post-COVID median of 10.70 (Q1= 9.00, Q3= 12.15), and 10.50 (Q1= 8.80, Q3= 12.35), respectively. In contrast, the difference was statistically significant among male participants (Z= -2.334, p = 0.02), with a pre- and post-COVID median of 10.20 (Q1= 8.70, Q3= 11.80), and 10.65 (Q1= 9.00, Q3= 12.70), respectively. There was a statistically significant increase in HbA1c of persons > 11 years old (Z= -2.471, p= 0.013), with a pre- and post-COVID median of 10.40 (Q1= 9.00, Q3= 12.10), and 10.90 (Q1= 9.00, Q3= 12.60), respectively. Conversely, persons ≤ 11 years old showed no statistically significant change in HbA1c (Z= -.457, p= 0.648), with a pre- and post-COVID median of 10.45 (Q1= 8.70, Q3= 11.85), and 10.20 (Q1= 8.40, Q3= 12.075), respectively. Disregarding any influence of time, the effect of sex showed no statistically significant difference in HbA1c between males and females [F (1,125) = 0.008, p = 0.930]. Meanwhile, the age effect on HbA1c, regardless of time influence, was statistically significant [F (1,125) = 4.993, p = 0.027]. There was no statistically significant interaction between time and sex on HbA1c levels [F (1.74, 217) = 0.096, p = 0.883] and between age and time [F (3.92,289.57) = 1.693, p = 0.190].CONCLUSIONSThe number of visits to healthcare facilities dropped significantly during the COVID-19 pandemic, but the rate of newly diagnosed T1DM increased. There was a variable effect on HbA1c levels of those patients, which suggests that each demographic group in the population might have been affected differently by the pandemic. Future research should determine factors associated with better glycemic control and measures to sustain these changes the pandemic might have created.