Founder effect and ancestral origin of the spinocerebellar ataxia type 7 (SCA7) mutation in Mexican families.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disease characterized by progressive cerebellar ataxia and macular degeneration causing progressive blindness. It accounts for 1 to 11.6 % of spinocerebellar ataxias (SCAs) cases worldwide and for 7.4 % of SCA7 cases in Mexico. We identified a cluster of SCA7 families who resided in a circumscribed area of Veracruz and investigated whether the high incidence of the disease in this region was due to a founder effect. A total of 181 individuals from 20 families were studied. Four microsatellite markers and one SNP flanking the ATNX7 gene were genotyped and the ancestral origin and local ancestry analysis of the SCA7 mutation were evaluated. Ninety individuals from 19 families had the SCA7 mutation; all were found to share a common haplotype, suggesting that the mutation in these families originated from a common ancestor. Ancestral origin and local ancestry analysis of SCA7 showed that the chromosomal segment containing the mutation was of European origin. We here present evidence strongly suggesting that the high frequency of SCA7 in Veracruz is due to a founder effect and that the mutation is most likely of European origin with greatest resemblance to the Finnish population.

Espectroscopia cuantitativa de hidrógeno por resonancia magnética de 3 T en pacientes sintomáticos y asintomáticos con enfermedad de Huntington / Hydrogen magnetic resonance quantitative spectroscopy at 3 T in symptomatic and asymptomatic Huntington’s disease patients

Introducción. La enfermedad de Huntington es un trastorno neurodegenerativo hereditario autosómico dominante, caracterizado por síntomas motores, cognitivos y psiquiátricos. Objetivo. Determinar si existen diferencias en las concentraciones de N-acetilaspartato, creatina y compuestos que contienen colina (glucerilfosforilcolina y fosfocolina) en el núcleo caudado, el putamen y la corteza occipital de pacientes con enfermedad de Huntington, sintomáticos y asintomáticos. Sujetos y métodos. Se realizaron estudios de espectroscopia de hidrógeno por resonancia magnética en un equipo de 3 T a 10 individuos con prueba genética para enfermedad de Huntington, incluidos en tres grupos: negativos (control), positivos sintomáticos y positivos asintomáticos. Los estudios se cuantificaron con LCModel y se analizaron mediante análisis de varianza y prueba de Fisher. Resultados. Los pacientes sintomáticos mostraron disminución de creatina y N-acetilaspartato en las regiones estudiadas, y disminución de colina en el putamen (p < 0,05). En el núcleo caudado se encontró diferencia de colina entre sintomáticos y asintomáticos (p < 0,05). Conclusiones. Los resultados reflejan disfunción en el metabolismo neuronal y sugieren que la creatina y la colina, al ser marcadores de membrana, pueden comportarse en forma indirecta como marcadores de la evolución en la enfermedad de Huntington (AU)

Introduction. Huntington’s disease is an hereditary autosomic-dominant neurodegenerative disorder, characterized by motor, cognitive and psychiatric symptoms. Aim. To quantify differences in N-acetylaspartate, creatine and choline in caudate nucleus, putamen and occipital cortex of patients with Huntington’s disease, symptomatics and asymptomatics. Subjects and methods. Hydrogen magnetic resonance spectroscopy was performed with a 3 T scanner in 10 Huntington’s disease gene-tested subjects, included in three groups: negative (control), positive sympomatics and positive asymptomatics. Data was quantified with LCModel and analyzed with ANOVA and Fisher tests. Results. Symptomatic patients showed decreased creatine and N-acetylaspartate in the three regions, and decreasedcholine only in putamen (p < 0.05). Choline difference was found between symptomatics and asymptomatics in the caudate nucleus (p < 0.05). Conclusions. Results may reflect neuronal dysfunction and suggest that creatine and choline may serve as markers for Huntington’s disease progression (AU)

[Hydrogen magnetic resonance quantitative spectroscopy at 3 T in symptomatic and asymptomatic Huntington's disease patients]. / Espectroscopia cuantitativa de hidrógeno por resonancia magnética de 3 T en pacientes sintomáticos y asintomáticoscon enfermedad de Huntington.

INTRODUCTION: Huntington's disease is an hereditary autosomic-dominant neurodegenerative disorder, characterized by motor, cognitive and psychiatric symptoms. AIM: To quantify differences in N-acetylaspartate, creatine and choline in caudate nucleus, putamen and occipital cortex of patients with Huntington's disease, symptomatics and asymptomatics. SUBJECTS AND METHODS: Hydrogen magnetic resonance spectroscopy was performed with a 3 T scanner in 10 Huntington's disease gene-tested subjects, included in three groups: negative (control), positive symptomatics and positive asymptomatics. Data was quantified with LCModel and analyzed with ANOVA and Fisher tests. RESULTS: Symptomatic patients showed decreased creatine and N-acetylaspartate in the three regions, and decreased choline only in putamen (p < 0.05). Choline difference was found between symptomatics and asymptomatics in the caudate nucleus (p < 0.05). CONCLUSIONS: Results may reflect neuronal dysfunction and suggest that creatine and choline may serve as markers for Huntington's disease progression.

[The absence of a relation between apolipoprotein E genotypes and the severity of multiple sclerosis in Mexican patients]. / Ausencia de relación entre los genotipos de apolipoproteína E y la gravedad de la esclerosis múltiple en pacientes mexicanos.

INTRODUCTION: The clinical course of multiple sclerosis (MS) varies widely. The natural history of the disease has shown that approximately 50% of patients that begin with a relapsing-remitting clinical course will have a progressive course about 10 years after disease onset and will need some kind of aid to walk. The expression of apolipoprotein E (ApoE) increases in nerve tissue undergoing regeneration and the ApoE epsilon-4 allele is associated with abnormal neural repair. Several different reports indicate that the ApoE epsilon-4 allele is associated with a greater progression of disability in patients with MS, although this is still a matter of debate. PATIENTS AND METHODS: We analyse the clinical characteristics of 99 patients diagnosed with MS, we describe the correlation between the presence or absence of the ApoE epsilon-4 allele and the age of onset, clinical subtype, progression of the disease, score on the Expanded Disability Status Scale and the relapse rate. We explore the impact of the presence of the epsilon-2 allele on the progress of the disease. RESULTS: In patients under 21 years of age, we observed a higher frequency of the presence of the epsilon-4 allele (p = 0.057). Nevertheless, no association was found between any of the ApoE alleles and the indices of disease progression. CONCLUSIONS: Our results do not suggest any association between the presence of the ApoE epsilon-4 allele and the progression of disability in patients with MS in our sample.

Ausencia de relación entre los genotipos de apolipoproteína E y la gravedad de la esclerosis múltiple en pacientes mexicanos / The absence of a relation between apolipoprotein E genotypes and the severity of multiple sclerosis

Introducción. El curso clínico de la esclerosis múltiple (EM) es muy variable. La historia natural de la enfermedad ha enseñado que aproximadamente el 50% de los pacientes que inician con un curso clínico brote-remisión tendrá un curso progresivo después de unos 10 años de evolución de la enfermedad y necesitará alguna ayuda para deambular. La expresión de la apolipoproteína E (ApoE) aumenta en el tejido nervioso en regeneración, y el alelo ApoE épsilon-4 está asociado con reparación neural anómala. Diversas comunicaciones indican que el alelo ApoE épsilon4 se asocia a una mayor progresión de la discapacidad en pacientes con EM, aunque es controvertido. Pacientes y métodos. Analizamos las características clínicas de 99 pacientes con diagnóstico de EM, describimos la correlación de la presencia o ausencia del alelo épsilon-4 de la ApoE con la edad de inicio, subtipo clínico, progresión de la enfermedad, puntuación de la Expanded Disability Status Scale y tasa de recaídas. Exploramos el impacto de la presencia del alelo épsilon-2 con la evolución de la enfermedad. Resultados. En pacientes menores de 21 años observamos una mayor frecuencia de la presencia del alelo épsilon-4 (p = 0,057), pero no encontramos ninguna asociación entre algún alelo de ApoE y los índices de progresión de la enfermedad. Conclusiones. Nuestros resultados no indican alguna asociación entre la presencia del alelo ApoE épsilon-4 en la progresión de discapacidad en pacientes con EM en nuestra muestra (AU)

Introduction. The clinical course of multiple sclerosis (MS) varies widely. The natural history of the disease has shown that approximately 50% of patients that begin with a relapsing-remitting clinical course will have a progressive course about 10 years after disease onset and will need some kind of aid to walk. The expression of apolipoprotein E (ApoE) increases in nerve tissue undergoing regeneration and the ApoE epsilon-4 allele is associated with abnormal neural repair. Several different reports indicate that the ApoE epsilon-4 allele is associated with a greater progression of disability in patients with MS, although this is still a matter of debate. Patients and methods. We analyse the clinical characteristics of 99 patients diagnosed with MS, we describe the correlation between the presence or absence of the ApoE epsilon-4 allele and the age of onset, clinical subtype, progression of the disease, score on the Expanded Disability Status Scale and the relapse rate. We explore the impact of the presence of the epsilon-2 allele on the progress of the disease. Results. In patients under 21 years of age, we observed a higher frequency of the presence of the epsilon-4 allele (p = 0.057). Nevertheless, no association was found between any of the ApoE alleles and the indices of disease progression. Conclusions. Our results do not suggest any association between the presence of the ApoE epsilon-4 allele and the progression of disability in patients with MS in our sample (AU)