Diagnóstico molecular de ataxias espinocerebelosas: reporte del primer caso de ataxia espinocerebelosa tipo 3 (SCA3) en Costa Rica confirmado por análisis molecular
Fecha
2017
Tipo
artículo original
Autores
Vásquez Cerdas, Melissa
Fernández Morales, Húberth
Cuenca Berger, Patricia
Morales Montero, Fernando
Título de la revista
ISSN de la revista
Título del volumen
Editor
Resumen
Antecedentes. Las ataxias hereditarias son un grupo de trastornos
genéticos caracterizados por descoordinación progresiva de la
marcha, a menudo asociada con una pobre coordinación de las
manos, el habla y los movimientos oculares. Dentro de las ataxias
hereditarias, están las ataxias espinocerebelosas (SCAs), que
comprenden un grupo de trastornos muy heterogéneo desde el
punto de vista clínico, patológico y genético.
Metodología. Un total de 20 pacientes con diagnóstico clínico
presuntivo de una SCA, fueron referidos al INISA con el propósito
de realizar estudios genéticos. Las ataxias tamizadas fueron las
de herencia autosómica dominante más frecuentes: SCA1, SCA2,
SCA3 y SCA6. El análisis molecular se llevó a cabo por medio de
la reacción en cadena de la polimerasa (PCR), electroforesis en
geles desnaturalizantes de urea-acrilamida con la posterior tinción
con nitrato de plata, y en algunos casos hibridación southern blot
(radioactivo) de los productos de PCR.
Resultados. Solamente en uno de los pacientes, con claros
antecedentes familiares, la prueba genética para la SCA3 dio
positiva. En los demás pacientes no se pudo confirmar a nivel
molecular el diagnóstico clínico.
Conclusiones. Este estudio representa un esfuerzo para establecer
en Costa Rica el diagnóstico molecular de algunas ataxias
hereditarias. El determinar la mutación causante de la ataxia tipo
3, nos permitió dar al paciente una clasificación clínica correcta y
brindarle el respectivo asesoramiento genético. Se evidencia una
considerable heterogeneidad etiológica entre las enfermedades
degenerativas con trastornos de la marcha, indicando la necesidad
de reevaluar clínicamente y de hacer estudios adicionales en los
demás pacientes.
Background. The hereditary ataxias are genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. There are a group of hereditary ataxias, the spinocerebellar ataxias (SCAs), which comprise a highly heterogeneous group from the clinical, pathological and genetic point of view. Methodology. A total of 20 patients with clinical diagnosis or suspect of SCA were referred to INISA for the purpose of performing genetic studies. The ataxias studied were the autosomal dominant ataxias most frequent: SCA1, SCA2, SCA3 and SCA6. Molecular analysis was carried out by polymerase chain reaction (PCR), electrophoresis on urea-acrylamide denaturing gels with subsequent silver nitrate staining, and in some cases southern blot (radioactive) hybridization of PCR products. Results. Only in one patient, with a clear family history, the genetic test for SCA3 was positive. In the other patients, the clinical diagnosis could not be confirmed at the molecular level. Conclusions. This study represents an effort to establish in Costa Rica the molecular diagnosis of some hereditary ataxias. Determining the causative mutation of type 3 ataxia allowed us to give the patient a correct clinical classification and provide the respective genetic counseling. There is a considerable etiological heterogeneity between degenerative diseases with gait disorders, indicating the need to reevaluate clinically and to perform additional studies in the other patients.
Background. The hereditary ataxias are genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. There are a group of hereditary ataxias, the spinocerebellar ataxias (SCAs), which comprise a highly heterogeneous group from the clinical, pathological and genetic point of view. Methodology. A total of 20 patients with clinical diagnosis or suspect of SCA were referred to INISA for the purpose of performing genetic studies. The ataxias studied were the autosomal dominant ataxias most frequent: SCA1, SCA2, SCA3 and SCA6. Molecular analysis was carried out by polymerase chain reaction (PCR), electrophoresis on urea-acrylamide denaturing gels with subsequent silver nitrate staining, and in some cases southern blot (radioactive) hybridization of PCR products. Results. Only in one patient, with a clear family history, the genetic test for SCA3 was positive. In the other patients, the clinical diagnosis could not be confirmed at the molecular level. Conclusions. This study represents an effort to establish in Costa Rica the molecular diagnosis of some hereditary ataxias. Determining the causative mutation of type 3 ataxia allowed us to give the patient a correct clinical classification and provide the respective genetic counseling. There is a considerable etiological heterogeneity between degenerative diseases with gait disorders, indicating the need to reevaluate clinically and to perform additional studies in the other patients.
Descripción
Palabras clave
DIAGNÓSTICO MOLECULAR, CASO CLÍNICO, COSTA RICA, ANÁLISIS MOLECULAR, GEN