Search

Background: Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. To date, mutations in 11 genes have been frequently associated with this phenotype. In Brazil, few cohorts have been screened for MODY, all using a candidate gene approach, with a high prevalence of undiagnosed cases (MODY-X)., Methods: We conducted a next-generation sequencing target panel (tNGS) study to investigate, for the first time, a Brazilian cohort of MODY patients with a negative prior genetic analysis. One hundred and two patients were selected, of which 26 had an initial clinical suspicion of MODY-GCK and 76 were non-GCK MODY., Results: After excluding all benign and likely benign variants and variants of uncertain significance, we were able to assign a genetic cause for 12.7% (13/102) of the probands. Three rare MODY subtypes were identified (PDX1/NEUROD1/ABCC8), and eight variants had not been previously described/mapped in genomic databases. Important clinical findings were evidenced in some cases after genetic diagnosis, such as MODY-PDX1/HNF1B., Conclusion: A multiloci genetic approach allowed the identification of rare MODY subtypes, reducing the large percentage of MODY-X in Brazilian cases and contributing to a better clinical, therapeutic, and prognostic characterization of these rare phenotypes., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Objectives: Despite the availability of a wide selection of anti-diabetic treatments, many type 2 DM (T2DM) patients still do not have controlled glucose levels. In addition to pharmacological intervention, patients' own implicit beliefs about their illness should be targeted for health intervention. Thus, we conducted a quantitative study to evaluate the associations between illness perception (IP) domains and metabolic control (HbA1c) of T2DM patients in Selama Hospital and to identify patients' perceptions of the causal T2DM factors., Method: A cross-sectional study was conducted in the outpatient department of Selama Hospital from October to December 2015. A total of 200 T2DM patients were recruited using systematic random sampling. A self-administered validated questionnaire consisting of three sections was used, and the data were analysed using SPSS version 18. The associations between eight IP domains and HbA1c were evaluated via multiple linear regression. P values <0.05 were considered significant., Key Findings: The analysis included data from 200 respondents with a mean age of 57.7 years (SE = 9.8). The majority were women (64.5%) and Malays (86%) with a primary school education (43.5%) and a family history of diabetes (53.5%). The median duration of illness was 5 years (IQR = 7), and the median HbA1c level was 8.15% (IQR = 3.1). The mean score for the eight IP domains was 33.7 (SE = 8.43) out of a total score of 80. Using multiple linear regression, HbA1c was found to be significantly associated with IP domains of identity symptoms at 0.221 (95% CI 0.083-0.358). Moreover, 79.4% of patients ranked diet and eating behaviour as the main factor for T2DM., Conclusion: The IP domain of identity symptoms was significantly correlated with T2DM metabolic control. By understanding patients' IP, healthcare providers can focus on behavioural approaches to managing T2DM patients. Steps must be taken to educate patients about the importance of diet control in managing T2DM., (© 2017 Royal Pharmaceutical Society.)

Maturity-Onset Diabetes of the Young (MODY) type 4 or PDX1 -MODY is a rare form of monogenic diabetes caused by heterozygous variants in PDX1 . Pancreatic developmental anomalies related to PDX1 are reported only in neonatal diabetes cases. Here, we describe dorsal pancreatic agenesis in 2 patients with PDX1 -MODY. The proband presented with diabetes since 14 years of age and maintained regular glycemic control with low doses of basal insulin and detectable C-peptide levels after 38 years with diabetes. A diagnosis of MODY was suspected. Targeted next-generation sequencing identified a heterozygous variant in PDX1 : c.188delC/p.Pro63Argfs*60. Computed tomography revealed caudal pancreatic agenesis. Low fecal elastase indicated exocrine insufficiency. His son had impaired glucose tolerance, presented similar pancreatic agenesis, and harbored the same allelic variant. The unusual presentation in this Brazilian family enabled expansion upon a rare disease phenotype, demonstrating the possibility of detecting pancreatic malformation even in cases of PDX1 -related diabetes diagnosed after the first year of life. This finding can improve the management of MODY4 patients, leading to precocious investigation of pancreatic dysgenesis and exocrine dysfunction., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. GCK -MODY and HNF1A -MODY are the prevalent subtypes. Currently, there is growing concern regarding the correct interpretation of molecular genetic findings. The American College of Medical Genetics and Genomics (ACMG) updated guidelines to interpret and classify molecular variants. This study aimed to determine the prevalence of MODY ( GCK / HNF1A ) in a large cohort of Brazilian families, to report variants related to phenotype, and to classify them according to ACMG guidelines. One hundred and nine probands were investigated, 45% with clinical suspicion of GCK -MODY and 55% with suspicion of HNF1A -MODY. Twenty-five different variants were identified in GCK gene (30 probands-61% of positivity), and 7 variants in HNF1A (10 probands-17% of positivity). Fourteen of them were novel (12- GCK /2- HNF1A ). ACMG guidelines were able to classify a large portion of variants as pathogenic (36%- GCK /86%- HNF1A ) and likely pathogenic (44%- GCK /14%- HNF1A ), with 16% (5/32) as uncertain significance. This allows us to determine the pathogenicity classification more efficiently, and also reinforces the suspected associations with the phenotype among novel variants., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The present study aimed to evaluate the prevalence of superficial lesions in the oral cavity mucosa in diabetic patients., Methods: The sample was made of 30 patients. To obtain these results we did rigorous clinical and complementary tests., Results: Of the 30 patients, 9 (30%) were males and 21 (70%) females. Of the studied patients, 40% were below 60 years of age, and 60% were older than 60 years. Thirteen different types of mucosal alterations were diagnosed. Tongue varicose veins (36.6%) and candidiasis (27.02%) were the most prevalent. Such alterations can be associated with the fact that these conditions are commonly found in senile patients and are also associated with prolonged wear of dentures. Xerostomia was diagnosed in only 1 (3.33%) patient, disagreeing with most of the studies observed in the literature., Conclusion: Most of the diabetic patients presented at least one type of oral mucosa lesion or alteration.