Genetics of Monogenic Diabetes: Present Clinical Challenges

Purpose of Review

Monogenic forms of diabetes have specific treatments that differ from the standard care provided for type 1 and type 2 diabetes, making the appropriate diagnosis essential. In this review, we discuss current clinical challenges that remain, including improving case-finding strategies, particularly those that have transethnic applicability, and understanding the interpretation of genetic variants as pathogenic, with clinically meaningful impacts.

Recent Findings

Biomarker approaches to the stratification for genetic testing now appear to be most effective in identifying cases of monogenic diabetes, and use of genetic risk scores may also prove useful. However, applicability in all ethnic groups is lacking. Challenges remain in the classification of genes as diabetes-causing and the interpretation of genetic variants at the clinical interface.

Summary

Since the discovery that genetic defects can cause neonatal or young-onset diabetes, multiple causal genes have been identified and there have been many advances in strategies to detect genetic forms of diabetes and their treatments. Approaches learnt from monogenic diabetes are now being translated to polygenic diabetes.

     

A Review on Joint Carotid Intima-Media Thickness and Plaque Area Measurement in Ultrasound for Cardiovascular/Stroke Risk Monitoring: Artificial Intelligence Framework

Journal of Digital Imaging - Cardiovascular diseases (CVDs) are the top ten leading causes of death worldwide. Atherosclerosis disease in the arteries is the main cause of the CVD, leading to...     

Pedicled Islanded Nasolabial Flap Tunneled Under Mandible for Tongue Reconstruction

BackgroundNasolabial flap is reliable flap in the reconstruction of oral defects over a period of time. Still there is scanty literature available of using this flap for reconstruction of isolated defects of tongue. We carried out this study in our patients to assess the role of pedicled nasolabial flap in reconstruction of isolated tongue defects.MethodsIn total, 11 patients with T1 and T2 tongue cancer were selected for the study. The functional improvement in the form of speech and swallowing was evaluated postoperatively.ResultsThe flap was successfully taken in all patients except for marginal or tip loss. This is a locally available flap with minimal operating time and does not require microvascular skills. The results of speech and swallowing after reconstruction were comparable.ConclusionNasolabial flap is an excellent locally available flap for the reconstruction of the anterior two-thirds of the tongue and with very minor, if any postoperative cosmetic defect.     

Genetic Abnormalities in FOXP1 Are Associated with Congenital Heart Defects

The etiology for the majority of congenital heart defects (CHD) is unknown. We identified a patient with unbalanced atrioventricular septal defect (AVSD) and hypoplastic left ventricle who harbored an ～0.3 Mb monoallelic deletion on chromosome 3p14.1. The deletion encompassed the first four exons of FOXP1, a gene critical for normal heart development that represses cardiomyocyte proliferation and expression of Nkx2.5. To determine whether FOXP1 mutations are found in patients with CHD, we sequenced FOXP1 in 82 patients with AVSD or hypoplastic left heart syndrome. We discovered two patients who harbored a heterozygous c.1702C>T variant in FOXP1 that predicted a potentially deleterious substitution of a highly conserved proline (p.Pro568Ser). This variant was not found in 287 controls but is present in dbSNP at a 0.2% frequency. The orthologous murine Foxp1 p.Pro596Ser mutant protein displayed deficits in luciferase reporter assays and resulted in increased proliferation and Nkx2.5 expression in cardiomyoblasts. Our data suggest that haploinsufficiency of FOXP1 is associated with human CHD.     

Improving Trauma Care in India: the Potential Role of the Rural Trauma Team Development Course (RTTDC)

The Rural Trauma Team Development Course (RTTDC) was devised to optimize trauma resuscitation training in under-resourced rural institutions. This program appears ideal for India because of its dense traffic, large population, and high frequency of rural trauma. We report on the feasibility and desirability of introducing RTTDC in India. An instructor course for 20 faculties and a provider course for 23 were conducted in New Delhi, India. The courses were evaluated by multiple choice question (MCQ) performance, by rating the modules on a three-point scale (1 = very relevant, 2 = relevant, and 3 = not relevant) for communication skills, principles of performance improvement and patient safety (PIPS), and clinical scenarios. Evaluation questionnaires including desirability of promulgation in India were completed using a five-point Likert Scale (1 = strongly agree, 2 = agree, 3 = neutral, 4 = disagree, and 5 = strongly disagree). Overall written comments were also provided. Both faculty and providers improved post-course MCQ scores (p?<?0.05) with lower scores in the provider group. Seventy-eight percent faculty and 74 % providers rated the communication module very relevant. PIPS was rated very relevant by 72 % faculty and 65 % providers. There were over 150 comments, generally positive with over 90 % of both faculty and providers rating strongly agree to agree that the course be promulgated widely in India. The RTTDC including plans for promulgation was enthusiastically received in India, and its potential for improving trauma care including communication skills and PIPS appears excellent.     

Multiple fistulae connecting the right coronary artery to the coronary sinus

Right coronary artery to coronary sinus fistula is a rare anomaly. We present a unique case of an adult patient with multiple fistulae from the right coronary artery draining into the coronary sinus near the posterior left atrium-left ventricle junction, first suspected by transthoracic two-dimensional echocardiography. The multiple openings were not seen by any invasive or noninvasive techniques and were noted only at the time of surgery. To our knowledge, this is the first case of multiple fistulae connecting the right coronary artery to the coronary sinus that has been reported in the English literature.