Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction.

BACKGROUND: Less than 40% of patients with dilated cardiomyopathy (DCM) have a pathogenic/likely pathogenic genetic variant identified. TBX20 has been linked to congenital heart defects; although an association with left ventricular noncompaction (LVNC) and DCM has been proposed, it is still considered a gene with limited evidence for these phenotypes. This study sought to investigate the association between the TBX20 truncating variant (TBX20tv) and DCM/LVNC. METHODS: TBX20 was sequenced by next-generation sequencing in 7463 unrelated probands with a diagnosis of DCM or LVNC, 22 773 probands of an internal comparison group (hypertrophic cardiomyopathy, channelopathies, or aortic diseases), and 124 098 external controls (individuals from the gnomAD database). Enrichment of TBX20tv in DCM/LVNC was calculated, cosegregation was determined in selected families, and clinical characteristics and outcomes were analyzed in carriers. RESULTS: TBX20tv was enriched in DCM/LVNC (24/7463; 0.32%) compared with internal (1/22 773; 0.004%) and external comparison groups (4/124 098; 0.003%), with odds ratios of 73.23 (95% CI, 9.90-541.45; P<0.0001) and 99.76 (95% CI, 34.60-287.62; P<0.0001), respectively. TBX20tv was cosegregated with DCM/LVNC phenotype in 21 families for a combined logarythm of the odds score of 4.53 (strong linkage). Among 57 individuals with TBX20tv (49.1% men; mean age, 35.9±20.8 years), 41 (71.9%) exhibited DCM/LVNC, of whom 14 (34.1%) had also congenital heart defects. After a median follow-up of 6.9 (95% CI, 25-75:3.6-14.5) years, 9.7% of patients with DCM/LVNC had end-stage heart failure events and 4.8% experienced malignant ventricular arrhythmias. CONCLUSIONS: TBX20tv is associated with DCM/LVNC; congenital heart defect is also present in around one-third of cases. TBX20tv-associated DCM/LVNC is characterized by a nonaggressive phenotype, with a low incidence of major cardiovascular events. TBX20 should be considered a definitive gene for DCM and LVNC and routinely included in genetic testing panels for these phenotypes.

Congenital hyperinsulinism in Gran Canaria, Canary Isles.

INTRODUCTION: Congenital hyperinsulinism (CH) is a severe disorder characterised by the appearance of severe hypoglycaemia. Pathogenic mutations in the ABCC8 and KCNJ11 genes are the most frequent cause, although its appearance also been associated to mutations in other genes (GCK, GLUD1, HADH, HNF1A, HNF4A, SLC16A1, UCP2, HK1), and with different syndromes. MATERIALS AND METHODS: Retrospective review of patients diagnosed with CH in this unit during the last 18 years (2001-2018). Genetic analysis included screening for 11 genes in genomic DNA from peripheral blood (ABCC8, GCK, GLUD1, HADH, HNF1A, HNF4A, INSR, KCNJ11, SLC16A1, UCP2, and SLC25A15). OBJECTIVE: To carry out a clinical and genetic characterisation of the diagnosed cases of CH in Gran Canaria. RESULTS: There have been 10 cases of persistent HC since 2001. Seven of them had mutations in the ABCC8 gene, one in the HNF4α gene, and in two patients, no pathogenic mutations were found in the analysed genes. Four patients presented with previously undescribed mutations. Pancreatectomy was performed in two of the cases. The minimum insulin value detected in hypoglycaemia was 6.81 µIU/mL. The incidence of persistent CH for Gran Canaria and Lanzarote is 1/15,614. CONCLUSIONS: Four patients had previously undescribed mutations. The most frequently affected gene was ABCC8. Pancreatectomy was required in 20% of the patients. An insulin value of ≥6.81 µIU/mL was observed in all patients at the time of diagnosis. The incidence of CH in Gran Canaria is high.

Adherence to Mediterranean diet is not associated with birthweight - Results form a sample of Canarian pregnant women.

INTRODUCTION: Background: the prevalence of overweight and obesity showed and increasing trend over the past few years. The burden of this epidemic represents a public health issue worldwide. Spain, and especially the Canary Islands, are not exempt. Pregnancy is a situation of weight gain, and the amount of such increase during gestation can affect the health status of both the mother and her baby. Thus, an optimal dietary style becomes of importance. Aim: given the benefits of the Mediterranean diet (MD) on various health outcomes, we aimed to study the adherence to this dietary pattern in a sample of Canarian pregnant women, and to investigate its association with their newborn's weight. Methods: adherence to MD as well as clinical history and anthropometrics were assessed in a sample of pregnant women followed at a Canarian hospital. Similarly, their newborn characteristics were studied. Results: our findings showed an overall low adherence to MD, with no association between this trend and birthweight. Conclusions: in conclusion, specific tools should be tailored to the target population to assess adherence to MD, and further efforts should be made to promote a healthy eating pattern and lifestyle among the pregnant population.

INTRODUCCIÓN: Introducción: la prevalencia del sobrepeso y la obesidad presentó una tendencia al alza en los últimos años. La carga de esta epidemia supone un problema de salud pública en todo el mundo. España, y especialmente las Islas Canarias, no es una excepción. El embarazo es una situación en la que se gana peso y la cantidad de peso que se gana durante la gestación puede afectar al estado de salud tanto de la madre como del niño. Por tanto, adquiere importancia seguir un tipo de dieta óptimo. Objetivo: dados los beneficios de la dieta mediterránea (DM) sobre varios resultados de salud, nos propusimos estudiar la adherencia a este patrón dietético en una muestra de embarazadas canarias e investigar su asociación con el peso neonatal. Métodos: la adherencia a la DM, al igual que la historia clínica y la antropometría, se evaluó en una muestra de mujeres embarazadas seguidas en un hospital canario. También se estudiaron las características de los neonatos. Resultados: nuestros hallazgos mostraron una adherencia general baja a la DM, sin ninguna asociación entre esta tendencia y el peso al nacer. Conclusiones: en conclusión, se deben adaptar a la población objeto de este estudio herramientas específicas que sirvan para evaluar la adherencia a la DM, y se deben realizar nuevos esfuerzos para fomentar un patrón alimenticio y un estilo de vida saludables entre la población gestante.