Edad de inicio y riesgo genético en la Ataxia espinocerebelosa tipo 2 / Age at onset and genetic risk for Spinocerebellar ataxia type 2

La Ataxia espinocerebelosa tipo 2 (SCA2) es una enfermedad neurodegenerativa que alcanza las mayores tasas de incidencia y de prevalencia en Holguín, Cuba. Obtener estimados probabilísticos del riesgo dependiente de la edad, de haber heredado la mutación causante de la SCA2. Fueron revisadas las historias clínicas de 748 pacientes afectados pertenecientes a 101 familias con SCA2. El diagnóstico molecular fue realizado por PCR. La edad de inicio promedio fue de 33 años, y el 50(percent) de los pacientes fueron asintomáticos antes de los 31 años de edad. El riesgo empírico fue del 50(per cent) para individuos con 7 años de edad o menos, pero en los casos con 65 años o más, el riesgo disminuyó hasta casi un 0(percent). Existe una disminución progresiva del riesgo genético para la SCA2 a medida que avanza la edad del individuo. Los resultados son presentados como un apoyo para el asesoramiento genético de individuos en riesgo…(AU)

Prism adaptation in spinocerebellar ataxia type 2.

Patients with spinocerebellar ataxia type 2 (SCA2), develop severe pontine nuclei, inferior olives, and Purkinje cell degeneration. This form of autosomal dominant cerebellar ataxia is accompanied by progressive ataxia and dysarthria. Although the motor dysfunction is well characterized in these patients, nothing is known about their motor learning capabilities. Here we tested 43 SCA2 patients and their matched controls in prism adaptation, a kind of visuomotor learning task. Our results show that their pattern of brain damage does not entirely disrupt motor learning. Rather, patients had impaired adaptation decrement, but surprisingly a normal aftereffect. Moreover, the mutation degree could discriminate the degree of adaptation. This pattern could reflect the net contribution of two adaptive mechanisms: strategic control and spatial realignment. Accordingly, SCA2 patients show an impaired strategic control that affects the adaptation rate, but a normal spatial realignment measured through the aftereffect. Our results suggest that the neural areas subserving spatial realignment are spared in this form of spinocerebellar ataxia.

Biología molecular de la enfermedad de Huntington / Huntingtons Disease Molecular Biology

La enfermedad de Huntington es un trastorno neurodegenerativo hereditario que se presenta por lo general en personas de mediana edad. Es progresiva y sus síntomas incluyen movimientos involuntarios de la cara y las extremidades, cambios en el estado de ánimo y una tendencia a perder la memoria. Se debe a la expansión de una secuencia repetitiva de CAG contenida en el gen IT15, que codifica para una proteína poliglutamínica con una manifiesta tendencia a formar agregados intra o peri-nucleares. El descubrimiento de la mutación causal de esta enfermedad ha hecho posible la implementación de programas para el diagnóstico molecular, presintomático y prenatal, así como un significativo avance en la comprensión de los mecanismos moleculares involucrados y la búsqueda de opciones terapéuticas. En el trabajo se realizó una revisión bibliográfica de la biología molecular de este síndrome...(AU)

Huntington´s disease is a hereditary and neurodegenerative syndrome which is frequently presented in middle aged people. It is progressive and its principal symptoms include face and extremities involuntary movements , changes in mood and loss of memory due to a CAG expansion in the IT15 gene for a polyglutamine protein with a trend to aggregation. The discovery of the causal mutation makes possible the implementation of molecular, predictive and prenatal diagnosis programs, as well as a significant improvement on the molecular mechanisms understanding that are involved, and the therapeutic options. A review on the molecular biology of this disease was carried out...(AU)

Prism adaptation in spinocerebellar ataxia type 2

Patients with spinocerebellar ataxia type 2 (SCA2), develop severe pontine nuclei, inferior olives, and Purkinje cell degeneration. This form ofautosomal dominant cerebellar ataxia is accompanied by progressive ataxia and dysarthria. Although the motor dysfunction is well characterizedin these patients, nothing is known about their motor learning capabilities. Here we tested 43 SCA2 patients and their matched controls in prismadaptation, a kind of visuomotor learning task. Our results show that their pattern of brain damage does not entirely disrupt motor learning. Rather,patients had impaired adaptation decrement, but surprisingly a normal aftereffect. Moreover, the mutation degree could discriminate the degreeof adaptation. This pattern could reflect the net contribution of two adaptive mechanisms: strategic control and spatial realignment. Accordingly,SCA2 patients show an impaired strategic control that affects the adaptation rate, but a normal spatial realignment measured through the aftereffect.Our results suggest that the neural areas subserving spatial realignment are spared in this form of spinocerebellar ataxia...(AU)

Spinocerebellar ataxia type 2 olfactoryimpairment shows a pattern similar toother major neurodegenerative diseases

Olfactory function isaffected in different neurodegenerativediseases. Recently, it hasbeen found that some hereditaryataxias are also associated withsignificant olfactory impairment.However, the initial findings didnot examine the nature of theolfactory impairment associatedwith these ataxias. In the presentarticle the effect of spinocerebellarataxia type 2 (SCA2) on olfactoryfunction was studied in 53 SCA2patients and 53 healthy controlsubjects from Holguý´n, Cuba.Several tests were applied to evaluateolfactory threshold, description,identification anddiscrimination. The results showsignificant impairment in SCA2patients on all olfactory measurements,and the pattern of olfactorydeficits found suggests that theyhave much in common with thosereported for other neurodegenerativediseases such as Parkinsonsand Alzheimers diseases...(AU)

Saccade velocity is controlled by polyglutamine size in spinocerebellar ataxia 2.

We assessed maximal saccade velocity (MSV) in 82 spinocerebellar ataxia type 2 (SCA2) patients and 80 controls, correlating it to disease duration, polyglutamine expansion size, age at onset, ataxia score, age, and sex. Little overlap with normal values was found even at earliest stages. Stepwise linear regression analysis showed that 60-degree MSV was strongly influenced by polyglutamine size and less by disease duration, whereas the reverse was found for ataxia score. Saccade velocity thus is a sensitive, quite specific, and objective endophenotype, useful to search polyglutamine modifier genes.

Saccade Velocity isControlled by PolyglutamineSize in SpinocerebellarAtaxia 2

We assessed maximal saccade velocity (MSV) in 82 spinocerebellarataxia type 2 (SCA2) patients and 80 controls,correlating it to disease duration, polyglutamine expansionsize, age at onset, ataxia score, age, and sex. Littleoverlap with normal values was found even at earlieststages. Stepwise linear regression analysis showed that 60-degree MSV was strongly influenced by polyglutaminesize and less by disease duration, whereas the reverse wasfound for ataxia score. Saccade velocity thus is a sensitive,quite specific, and objective endophenotype, useful tosearch polyglutamine modifier genes...(AU)