PDX1-MODY: A rare missense mutation as a cause of monogenic diabetes

Maturity-Onset Diabetes of the Young type 4 is a rare form of diabetes mellitus, caused by mutations in the PDX1 gene. However, only a few mutations in this gene have been associated as a cause of monogenic diabetes up to date. It makes difficult to create a clinical manifestation profile of this disease and, consequently, to improve the therapeutic management for these patients. Here we report a normal weight woman, diagnosed with diabetes mellitus at 27 years old, during her first pregnancy. At the time of the recruitment, she was 40 years old and had a body mass index of 23.9 kg/m², glycated hemoglobin level of 9.6%, and fasting plasma glucose (FPG) of 254 mg/dL. She presented no diabetic complications and she was being treated with insulin. She reported a family history of diabetes mellitus characteristic of an autosomal dominant mode of inheritance. Molecular analysis of the PDX1 gene revealed the missense variant c.532G > A (p.(Glu178Lys)) segregating from the patient to her son, reported as diabetic. It was absent in her healthy daughter. The c.532G > A seems to be a rare variant, absent in human variants databases, and among 86 normoglycemic controls. Eight in silico algorithms classified this variant as probably pathogenic. Additionally, analysis of the evolutionary conservation showed the glutamic acid in the position 178 of PDX-1 protein as conserved among several species. Our findings reinforce the importance of screening rare MODY genes among families with suspicion of monogenic diabetes to help better understand the clinical manifestations of this disease.     

How is the quality of the available evidence on molar-incisor hypomineralization treatment? An overview of systematic reviews

Clinical Oral Investigations - This overview analyzed the quality of the systematic reviews (SRs) available on treatments for molar-incisor hypomineralization (MIH). Six electronic databases were...     

Ecological study of gastric cancer in Brazil:Geographic and time trend analysis

AIM:To investigate the geographic distributions and time trends of gastric cancer(GC)incidence and mortality in Brazil.METHODS:An ecological study of the DATASUS registry was conducted by identifying hospitalizations for GC between January 2005 and December 2010.The data included information on the gender,age,and town of residence at the time of hospital admission and death.RESULTS:The GC rates,adjusted according to available hospital beds,decreased from 13.8 per 100000in 2005 to 12.7 per 100000 in 2010.The GC rates decreased more among the younger age groups,in which the male-to-female difference also decreased in comparison to the older age groups.Although the lethality rates tended to increase with age,young patients were proportionally more affected.The spatial GC distribution showed that the rates were higher in the south and southeast.However,while the rates decreased in the central-west and south,they increased in the northern regions.A geographic analysis showed higher rates of GC in more urbanized areas,with a coast-toinland gradient.Geographically,GC lethality overlapped greatly with the hospital admission rates.CONCLUSION:The results of this study support the hypothesis of a critical role for environmental factors in GC pathogenesis.The declining rates in young patients,particularly males,suggest a relatively recent decrease in the exposure to risk factors associated with GC.The spatial distribution of GC indicates an ongoing dynamic change within the Brazilian environment.