Miguel Ángel Montes Navarro

Mutation in JPH2 cause dilated cardiomyopathy.

Recent studies have begun to uncover whether mutations in the JPH2 gene are associated with hypertrophic cardiomyopathy; however, this association is supported by very few reports and familial segregation studies are not always available (1–3). At present, there is no report to support the relationship between mutations in the JPH2 gene and the development of dilated cardiomyopathy (DCM). Fig. 1a summarizes all published mutations in JPH2, together with their protein location and clinical phenotype. In this study, we describe a novel mutation in JPH2 which suggests for the first time that JPH2 could cause DCM. Two novel variants were identified by ultrasequencing in the index case of a family with DCM: the p.Asn1474Lys variant in the SCN5A gene and the p.Glu85Lys variant in the JPH2 gene (Fig. 1b). These variants had not been previously described or published in any genetic databases (dbSNP from NCBI, Exome Sequencing Project of NHLBI). Mutations in the SCN5A gene have been related to the development of DCM. In silico analysis from the pathogenicity study classified these as variants of unknown significance (VUS2) (4). A total of 12 family members (10 males, 83.3%), 9 of them carriers of p.Glu85Lys in the JPH2 gene, were studied (Figure S1), being 7 affected. Two of the affected had also the p.Asn1474Lys variant in the SCN5A gene (II.3 and III.2). A high penetrance for the p.Glu85Lys mutation (77.7%) and a 100% co-segregation with the disease led to classification of p.Glu85Lys as pathogenic. p.Asn1474Lys did not co-segregate with the disease in the family. Mean age of diagnosis was 39 years old (younger aged 12 years). The proband (II.3), was a 51-year-old man, who was referred for evaluation with symptoms of heart failure. Echocardiography revealed severe left ventricular (LV) dilatation with moderate systolic dysfunction, grade III diastolic dysfunction (Table S1, Supporting Information). During follow-up, right ventricular (RV) dilatation and dysfunction developed. After 7 years of initial diagnosis, he was admitted to the hospital with a complete atrioventricular block (third-AVB). Taking into account the patient’s adverse clinical course despite optimal medical treatment, a biventricular pacemaker-ICD was implanted. Clinical study of relatives revealed that the proband’s son (III.2), an asymptomatic recreational athlete, had findings of DCM with moderate LV dilatation and mild systolic dysfunction. The proband’s brother (II.6), aged 65 years, had severe LV dilatation and systolic dysfunction. Coronary angiogram showed severe right coronary stenosis, which was stented. His two sons (III.4 and III.6), 39 and 37 years old athletes showed pathological Q waves in precordial leads (V1–V3) not explained by physiological adaptation to exercise together with LV dilatation and systolic dysfunction (Table S1). Two grandsons (sons of III.4) were also carriers of p.Glu85Lys mutation, being the oldest (aged 12 years) affected by the disease. His ECG showed a first degree AVB and mild bi-ventricular systolic dysfunction. The youngest brother of the proband (II.8) aged 49 years, had more advanced disease with LV systolic dysfunction, severe mitral and tricuspid regurgitation, and severe pulmonary hypertension. He underwent cardiac transplantation at the age of 60 years old. His son (III.8) was studied at the age of 31 and was found to be normal. Of note, prominent trabeculations involving the mid-apex at the antero-inferolateral wall were found in five patients, two of them (II.3 and II.6) fulfilled LV non-compaction (LVNC) criteria (Figure S2). In addition, none of the JPH2 mutation carriers with available cardiac magnetic resonance showed delayed gadolinium enhancement suggestive of myocardial fibrosis (Table S1). Regarding to conduction and rhythm disturbances, most of the affected members presented with various degrees of conduction disease requiring pacemaker implantation in two cases. None of the affected had atrial or ventricular arrhythmias on holter or stress testing except for III.6 who had a NSVT on 24 h-Holter monitoring. p.Glu85Lys in JPH2 affects a highly conserved amino acid, which is located in the MORN 4 motif (amino acids 82 – 104) that belongs to the large N-terminal cytoplasmic region of Junctophilin. The function of this domain is presently unknown. MORN motifs are highly conserved across isoforms and species contributing to plasma membrane binding, suggesting that these domains are essential for JPH2 function and play a critical role in the maintenance of effective Ca2+-handling. Some authors have reported the mechanisms by which JPH2 mutations that affects the junctional plasma membrane complex might have a role in sarcoplasmic reticulum Ca2+ release, suggesting involvement in excitation–contraction process (3, 5). In our study, none of the three carriers of p.Glu85Lys who developed severe systolic impairment

Conocimiento de aritmética de futuros maestros. Debilidades y fortalezas

Los medios de comunicacion han alertado recientemente a la opinion publica acerca de una realidad que la investigacion en educacion matematica llevaba evidenciando las dos ultimas decadas: la deficiente formacion matematica de los maestros. Estas deficiencias, que habiamos venido constatando de manera informal en nuestras universidades con los estudiantes para Maestro (EPM), son el objeto de estudio de nuestra investigacion. En ese contexto, este articulo describe un estudio exploratorio tipo survey sobre el conocimiento matematico necesario para la ensenanza que tienen 737 estudiantes para Maestro de tres centros de formacion de maestros de universidades andaluzas, realizado en el contexto de un Proyecto de Innovacion Docente de una de ellas. Usando el marco de conocimiento especializado del profesor de Matematicas (MTSK) y, dentro de el, el subdominio relativo al conocimiento de los temas matematicos, se elaboro un cuestionario que contenia items relativos a fracciones, decimales y porcentajes, contenidos que fueron elegidos tanto por su trascendencia intrinseca como por su aplicacion a otros contenidos matematicos y a otras disciplinas en el ambito de la Educacion Primaria. Esto nos ha permitido explorar el conocimiento que estos futuros profesores poseen sobre esos contenidos. Los resultados han mostrado un numero importante de debilidades, algunas de las cuales ya habian sido descritas por la literatura de investigacion, y tambien algunas fortalezas. En ambos casos, la informacion obtenida supone un referente para explorar la realidad de otros centros de formacion de maestros; un elemento de reflexion para las autoridades academicas acerca de los procesos de seleccion para el acceso a la universidad y, mas concretamente, a estos centros de formacion; y un punto de partida para el rediseno de sus programas de formacion.The social media have recently warned to public opinion about a truth that the research in mathematics education has been pointing up the last two decades: the poor mathematical training of primary teachers. These deficiencies, that we have being noticing in our universities with the prospective primary teachers (PPT), are our object of study. In this context, this paper describes a survey-type study on the mathematical knowledge required to teach of 737 prospective primary teachers from three universities in Andalusia. Based on the Mathematic Teacher Specialized Knowledge (MTSK), we have carried out a questionnaire addressing items related to fractions, decimals and percentages, contents chosen by its intrinsic transcendence, as by their application to other mathematical contents and other disciplines, in the ambit of primary school. This questionnaire has allowed us to explore the knowledge that these future teachers posses about these contents. The results of the study show an important number of weaknesses, some of them already described in research literature, and also some strengths. In both cases, the obtained information gives a base to explore other teacher training centers, elements of reflection to the academic authorities about the selection process to the access to university and, more concretely, to this training centers, as a starting point to redesign their training programs.

The arithmetic Knowledge of prospective teacher : strengths and weaknesses

Los medios de comunicacion han alertado recientemente a la opinion publica acerca de una realidad que la investigacion en educacion matematica llevaba evidenciando las dos ultimas decadas: la deficiente formacion matematica de los maestros. Estas deficiencias, que habiamos venido constatando de manera informal en nuestras universidades con los estudiantes para Maestro (EPM), son el objeto de estudio de nuestra investigacion. En ese contexto, este articulo describe un estudio exploratorio tipo survey sobre el conocimiento matematico necesario para la ensenanza que tienen 737 estudiantes para Maestro de tres centros de formacion de maestros de universidades andaluzas, realizado en el contexto de un Proyecto de Innovacion Docente de una de ellas. Usando el marco de conocimiento especializado del profesor de Matematicas (MTSK) y, dentro de el, el subdominio relativo al conocimiento de los temas matematicos, se elaboro un cuestionario que contenia items relativos a fracciones, decimales y porcentajes, contenidos que fueron elegidos tanto por su trascendencia intrinseca como por su aplicacion a otros contenidos matematicos y a otras disciplinas en el ambito de la Educacion Primaria. Esto nos ha permitido explorar el conocimiento que estos futuros profesores poseen sobre esos contenidos. Los resultados han mostrado un numero importante de debilidades, algunas de las cuales ya habian sido descritas por la literatura de investigacion, y tambien algunas fortalezas. En ambos casos, la informacion obtenida supone un referente para explorar la realidad de otros centros de formacion de maestros; un elemento de reflexion para las autoridades academicas acerca de los procesos de seleccion para el acceso a la universidad y, mas concretamente, a estos centros de formacion; y un punto de partida para el rediseno de sus programas de formacion.The social media have recently warned to public opinion about a truth that the research in mathematics education has been pointing up the last two decades: the poor mathematical training of primary teachers. These deficiencies, that we have being noticing in our universities with the prospective primary teachers (PPT), are our object of study. In this context, this paper describes a survey-type study on the mathematical knowledge required to teach of 737 prospective primary teachers from three universities in Andalusia. Based on the Mathematic Teacher Specialized Knowledge (MTSK), we have carried out a questionnaire addressing items related to fractions, decimals and percentages, contents chosen by its intrinsic transcendence, as by their application to other mathematical contents and other disciplines, in the ambit of primary school. This questionnaire has allowed us to explore the knowledge that these future teachers posses about these contents. The results of the study show an important number of weaknesses, some of them already described in research literature, and also some strengths. In both cases, the obtained information gives a base to explore other teacher training centers, elements of reflection to the academic authorities about the selection process to the access to university and, more concretely, to this training centers, as a starting point to redesign their training programs.