Association between the Mediterranean diet and metabolic syndrome with serum levels of miRNA in morbid obesity

Background: The Mediterranean diet (MD) could be involved in the regulation of different miRNAs related to metabolic syndrome (MS). Methods: We analyzed the serum level of mir-let7a-5p, mir-21, mir-590, mir-107 and mir-192 in patients with morbid obesity and its association with the MD and MS. Results: There is an association between the adherence to MD and higher serum levels of mir-590. Mir-590 was lower in those patients who consumed >2 commercial pastries/week. Mir-let7a was lower in those who consumed ≥1 sweetened drinks, in those who consumed ≥3 pieces of fruit/day and in those who consumed less red than white meat. A lower mir-590 and mir-let7a, and a higher mir-192 level, were found in patients who met the high-density lipoprotein cholesterol (HDL) criterion of MS. A higher mir-192 was found in those patients who met the triglyceride criterion of MS and in those with type 2 diabetes (T2DM). Conclusions: There is an association between specific serum levels of miRNAs and the amount and kind of food intake related to MD. Mir-590 was positively associated with a healthy metabolic profile and type of diet, while mir-192 was positively associated with a worse metabolic profile. These associations could be suggestive of a possible modulation of these miRNAs by food

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy

BACKGROUND: The genetic cause of hypertrophic cardiomyopathy remains unexplained in a substantial proportion of cases. Formin homology 2 domain containing 3 (FHOD3) may have a role in the pathogenesis of cardiac hypertrophy but has not been implicated in hypertrophic cardiomyopathy. OBJECTIVES: This study sought to investigate the relation between FHOD3 mutations and the development of hypertrophic cardiomyopathy. METHODS: FHOD3 was sequenced by massive parallel sequencing in 3,189 hypertrophic cardiomyopathy unrelated probands and 2,777 patients with no evidence of cardiomyopathy (disease control subjects). The authors evaluated protein-altering candidate variants in FHOD3 for cosegregation, clinical characteristics, and outcomes. RESULTS: The authors identified 94 candidate variants in 132 probands. The variants' frequencies were significantly higher in patients with hypertrophic cardiomyopathy (74 of 3,189 [2.32%]) than in disease control subjects (18 of 2,777 [0.65%]; p < 0.001) or in the gnomAD database (1,049 of 138,606 [0.76%]; p < 0.001). FHOD3 mutations cosegregated with hypertrophic cardiomyopathy in 17 families, with a combined logarithm of the odds score of 7.92, indicative of very strong segregation. One-half of the disease-causing variants were clustered in a small conserved coiled-coil domain (amino acids 622 to 655); odds ratio for hypertrophic cardiomyopathy was 21.8 versus disease control subjects (95% confidence interval: 1.3 to 37.9; p < 0.001) and 14.1 against gnomAD (95% confidence interval: 6.9 to 28.7; p < 0.001). Hypertrophic cardiomyopathy patients carrying (likely) pathogenic mutations in FHOD3 (n = 70) were diagnosed after age 30 years (mean 46.1 ± 18.7 years), and two-thirds (66%) were males. Of the patients, 82% had asymmetric septal hypertrophy (mean 18.8 ± 5 mm); left ventricular ejection fraction <50% was present in 14% and hypertrabeculation in 16%. Events were rare before age 30 years, with an annual cardiovascular death incidence of 1% during follow-up. CONCLUSIONS: FHOD3 is a novel disease gene in hypertrophic cardiomyopathy, accounting for approximately 1% to 2% of cases. The phenotype and the rate of cardiovascular events are similar to those reported in unselected cohorts. The FHOD3 gene should be routinely included in hypertrophic cardiomyopathy genetic testing panels

Nutrición parenteral domiciliaria en España 2018. Informe del Grupo de Nutrición Artificial Domiciliaria y Ambulatoria NADYA

Objetivo: comunicar los datos de nutrición parenteral domiciliaria (NPD) obtenidos del registro del grupo NADYA-SENPE (www.nadya-senpe.com) del año 2018. Material y métodos: análisis descriptivo de los datos recogidos de pacientes adultos y pediátricos con NPD en el registro NADYA-SENPE del 1 de enero al 31 de diciembre de 2018. Resultados: se registraron 278 pacientes (54, 7% mujeres), 23 niños y 255 adultos, procedentes de 45 hospitales españoles, lo que representa una tasa de prevalencia de 5, 95 pacientes/millón de habitantes/año 2018. El diagnóstico más frecuente en adultos fue “oncológico paliativo” (22, 0%), seguido de “otros”. En niños fue la enfermedad de Hirschsprung junto con la enterocolitis necrotizante, con cuatro casos (17, 4%). El primer motivo de indicación fue síndrome de intestino corto tanto en niños (60, 9%) como en adultos (35, 7%). El tipo de catéter más utilizado fue el tunelizado tanto en niños (81, 0%) como en adultos (41, 1%). Finalizaron 75 episodios, la causa más frecuente fue el fallecimiento (52, 0%) y el paso a vía oral (33, 3%). Conclusiones: el número de centros y profesionales colaboradores en el registro de pacientes que reciben NPD se mantiene estable, así como las principales indicaciones y los motivos de finalización de la NPD. Aim: To communicate home parenteral nutrition (HPN) data obtained from the HPN registry of the NADYA-SENPE group (www.nadya-senpe.  com) for the year 2018. Material and methods: Descriptive analysis of the data collected from adult and pediatric patients with HPN in the NADYA-SENPE group registry from January 1st, 2018 to December 31st, 2018.  Results: There were 278 patients from 45 Spanish hospitals (54.7% women), 23 children and 255 adults, which represent a prevalence rate of 5.95 patients/million inhabitants/year 2018. The most frequent diagnosis in adults was “palliative cancer” (22.0%), followed by “others”. In children it was Hirschsprung’s disease together with necrotizing enterocolitis, with four cases (17.4%). The first indication was short bowel syndrome in both children (60.9%) and adults (35.7%). The most frequently used type of catheter was tunneled in both children (81.0%) and adults (41.1%). Ending 75 episodes, the most frequent cause was death (52.0%) and change to oral feeding (33.3%). Conclusions: The number of centers and collaborating professionals in the registry of patients receiving HPN remains stable, as well as the main indications and reasons for termination of HPN

Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy.

The genetic cause of hypertrophic cardiomyopathy remains unexplained in a substantial proportion of cases. Formin homology 2 domain containing 3 (FHOD3) may have a role in the pathogenesis of cardiac hypertrophy but has not been implicated in hypertrophic cardiomyopathy. This study sought to investigate the relation between FHOD3 mutations and the development of hypertrophic cardiomyopathy. FHOD3 was sequenced by massive parallel sequencing in 3,189 hypertrophic cardiomyopathy unrelated probands and 2,777 patients with no evidence of cardiomyopathy (disease control subjects). The authors evaluated protein-altering candidate variants in FHOD3 for cosegregation, clinical characteristics, and outcomes. The authors identified 94 candidate variants in 132 probands. The variants' frequencies were significantly higher in patients with hypertrophic cardiomyopathy (74 of 3,189 [2.32%]) than in disease control subjects (18 of 2,777 [0.65%]; p  FHOD3 is a novel disease gene in hypertrophic cardiomyopathy, accounting for approximately 1% to 2% of cases. The phenotype and the rate of cardiovascular events are similar to those reported in unselected cohorts. The FHOD3 gene should be routinely included in hypertrophic cardiomyopathy genetic testing panels

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G &gt; T (p.Arg1129Leu) in ABCA4 and c.2276G &gt; T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations