RESUMO
Background and Objectives: To determine the diagnostic efficacy of clinical exome-targeted sequencing (CES) and spinocerebellar ataxia 36 (SCA36) screening in a real-life cohort of patients with cerebellar ataxia (CA) from Eastern Spain. Methods: A total of 130 unrelated patients with CA, negative for common trinucleotide repeat expansions (SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, dentatorubral pallidoluysian atrophy [DRPLA], and Friedreich ataxia), were studied with CES. Bioinformatic and genotype-phenotype analyses were performed to assess the pathogenicity of the variants encountered. Copy number variants were analyzed when appropriate. In undiagnosed dominant and sporadic cases, repeat primed PCR was used to screen for the presence of a repeat expansion in the NOP56 gene. Results: CES identified pathogenic or likely pathogenic variants in 50 families (39%), including 23 novel variants. Overall, there was a high genetic heterogeneity, and the most frequent genetic diagnosis was SPG7 (n = 15), followed by SETX (n = 6), CACNA1A (n = 5), POLR3A (n = 4), and SYNE1 (n = 3). In addition, 17 families displayed likely pathogenic/pathogenic variants in 14 different genes: KCND3 (n = 2), KIF1C (n = 2), CYP27A1A (n = 2), AFG3L2 (n = 1), ANO10 (n = 1), CAPN1 (n = 1), CWF19L1 (n = 1), ITPR1 (n = 1), KCNA1 (n = 1), OPA1 (n = 1), PNPLA6 (n = 1), SPG11 (n = 1), SPTBN2 (n = 1), and TPP1 (n = 1). Twenty-two novel variants were characterized. SCA36 was diagnosed in 11 families, all with autosomal dominant (AD) presentation. SCA36 screening increased the total diagnostic rate to 47% (n = 61/130). Ultimately, undiagnosed patients showed delayed age at onset (p < 0.05) and were more frequently sporadic. Discussion: Our study provides insight into the genetic landscape of CA in Eastern Spain. Although CES was an effective approach to capture genetic heterogeneity, most patients remained undiagnosed. SCA36 was found to be a relatively frequent form and, therefore, should be tested prior to CES in familial AD presentations in particular geographical regions.
RESUMO
RESUMEN Introducción: Se realizó una investigación de desarrollo tecnológico en el período 2019-2020 en Previsora, comunidad urbana, de Camagüey. Su ejecución fue liderada por investigadores y profesionales de enfermería comunitaria. El objetivo del presente trabajo está dirigido a caracterizar la comunidad desde la perspectiva histórico social y de salud para la identificación de las necesidades de aprendizaje de los profesionales de enfermería comunitaria. Métodos: Se realizó un estudio etnográfico como método de recopilación descriptivo de datos a partir de la combinación de técnicas y fuentes; de ellas se especifica: grupos focales, entrevista a profundidad, entrevista estructurada abierta y la observación participante y dentro del método cuantitativo: entrevista estructurada cerrada; así como los elementos más significativos del Análisis de la Situación de salud. Se realizó una triangulación teórica y metodológica de técnicas, instrumentos y fuentes en correspondencia con la metodología cualitativa y cuantitativa, según el momento de la investigación. Resultados: Se evidenció falta de sentido de pertenencia de los pobladores, indisciplinas sociales que perjudican la comunidad y su salud, deterioro de las relaciones interpersonales, sistema eco cultural deficiente y se identificó la necesidad de emprender otras acciones comunitarias que inciten el cambio y modifiquen el cuadro de salud comunitaria. Discusión: Los resultados que se exhiben coinciden con los de investigaciones desarrolladas por prestigiosos profesionales de las ciencias sociales y humanísticas.
ABSTRACT Introduction: A technological développent investigation was carried out in the period 2019-2020 in Previsora, an urban community, in Camagüey. Its execution was led by researchers and community nursing professionals. The objective of this work is aimed at characterizing the community from a historical, social and health perspective in order to identify the learning needs of community nursing professionals. Methods: An ethnographic study was carried out as a method of descriptive data collection from the combination of techniques and sources; of them are specified: focus groups, in-depth interview, open structured interview and participant observation and within the quantitative method: closed structured interview; as well as the most significant elements of the Health Situation Analysis. A theoretical and methodological triangulation of techniques, instruments and sources was carried out in correspondence with the qualitative and quantitative methodology, according to the moment of the investigation. Results: Lack of sense of belonging of the inhabitants was evidenced, social indiscipline that harms the community and its health, deterioration of interpersonal relationships, deficient eco-cultural system and it was identified the need to undertake other community actions that incite change the environment and modify the community health chart. Discussion: The results that are exhibited coincide with those of research carried out by prestigious professionals in the social and humanistic sciences.
