Migraña con aura: Una mirada molecular a un problema hereditario / Migraine with aura: A molecular view to a hereditary disorder

Migraine with aura (MA) is a common neurological disorder characterized by severe episodes of headache, generally unilateral, which are preceded by a focal reversible neurological deficit. The studies on MA reveal the existence of familiar aggregation compatible with a high degree of heritability and a complex multifactorial mode of transmission. The genetic factors of MA are unknown. An association to a locus in the long arm of chromosome 4 at the level of 4q22-q25 was recently reported in families with MA in Finland. Objetive: To analyze the genomic DNA of 5 Chilean families with MA to determine if there is linkage to the locus described in Finish families. Metodology: Families with MA were selected applying the diagnostic criteria of the International Headache Society (ICD-10), in which the index case or a member of the family should have MA. The genomic DNA was extracted from peripheral lymphocytes of members of each family (n = 25). Highly polymorphic genomic markers were used for the systematic analysis of the locus on 4q22-q25. Results and Discussion: The LOD score analysis of the 5 Chilean families investigated showed absence of linkage to the marker D4S1578 (maximum 0,35; p = 0.24). Due to the complexity of MA heritability it is possible that one or more loci different from the studied region are involved in the pathophysiology of MA. The study will continue with the inclusion of more family members and isolated MA cases, with the purpose of comparing Chilean and German families in an independent sample.

La migraña con aura (MA) es una patología común, caracterizada por ataques severos de cefalea generalmente unilateral, precedidos por un déficit neurológico focal reversible. Los estudios en MA revelan la existencia de agregación familiar compatible con un alto grado de herencia y un modo de transmisión multifactorial complejo. Los factores genéticos de la MA con herencia compleja son desconocidos. En familias finlandesas con MA se encontró recientemente ligamiento a un locus en el brazo largo del cromosoma 4 a nivel de 4q22-q25. Objetivo: Analizar el DNA genómico de 5 familias chilenas con MA para determinar si hay ligamiento al locus descrito en familias finlandesas. Metodología: Se seleccionaron familias con MA aplicando los criterios diagnósticos de la Sociedad Internacional de Cefalea (ICD-10), donde el caso índice o algún miembro de la familia debían tener MA. El DNA genómico se extrajo de leucocitos en sangre periférica de miembros seleccionados de cada familia (n = 25). Se usaron marcadores genómicos altamente polimórficos (microsatélites) para el análisis sistemático del locus 4q22-q25. Resultados y Discusión: El cálculo del LOD score mostró ausencia de ligamiento en las 5 familias analizadas (máximo de 0,35; p = 0,24) con el marcador D4S1578. Dado el carácter complejo de herencia en la MA es posible que existan uno o varios loci involucrados en su etiopatogenia, distintos al de la región estudiada. El estudio se continuará a través de la ampliación de las familias estudiadas y de la recolección de casos aislados de MA, con el objetivo de realizar futuros estudios de asociación para comparar los hallazgos en familias chilenas con los de familias alemanas en una muestra independiente.

Diagnóstico molecular de los síndromes de Prader-Willi y de Angelman: análisis de metilación, citogenética y FISH / Methylation, citogenetic and FISH tests in the molecular diagnosis of Prader-Willi and Angelman syndromes

Background: The diagnosis of Prader-Willi and Angelman syndromes is difficult, since their phenotypic manifestations are variable and unspecific. The study of the methylation state of DNA in l5(q11-q13) using polymerase chain reaction, called methylation test, allows the diagnosis of most patients with Prader-Willi and Angelman syndromes, irrespective if the underlying molecular alteration is a deletion, uniparental disomy or a punctual imprinting mutation. Aim: To assess the effectiveness of methylation test in the diagnosis of Prader-Willi and Angelman syndromes. Patients and methods : Thirty seven cases with a presumptive diagnosis of Prader-Willi syndrome and 25 with the presumptive diagnosis of Angelman syndrome were studied. Methylation test was done in genomic DNA obtained from peripheral Iymphocytes. Results: Methylation test confirmed the clinical diagnosis in 11 of 37 patients with PraderWilli (30 percent) and 6 of 25 patients with Angelman syndrome (24 percent). Conclusions: Clinical criteria overestimate the diagnosis of Prader-Willi and Angelman syndromes. The initial diagnosis should be confirmed with the methylation test and, if necessary, with FISH that will detect most deletions in the region

Nutrición molecular, papel del sistema PPAR en el metabolismo lipídico y su importancia en obesidad y diabetes mellitus / Molecular nutrition: regulation of lipid metabolism by peroxisome proliferator activated receptors, PPAR: their relatioship to obesity and diabetes mellitus

PPARs are transcription factors belonging to the super family of hormonal receptors. Their activity is regulated by fibrates, thiazolidinediones, certain anti inflammatory drugs and fatty acid derivatives, present in food. PPAR isoforms play a central role in lipid homeostasis, regulating anabolic (PPARg) and catabolic (PPARa) pathways of lipid metabolism. Additionally, these receptors participate in glucose homeostasis, influence cellular proliferation and differentiation and participate in inflammatory processes. The effects of PPARs on oxidative substrate partitioning suggests that they have a relevant role in the development of obesity and insulin resistance

Análisis molecular directo de mutaciones en el gen FMR-1 en pacientes con síndrome de Xq frágil y sus familias / Direct molecular analysis of FMR-1 gene mutation in patients with fragile Xq syndrome and their families

Background: The unequivocal diagnosis of fragile Xq syndrome is based in the direct analysis of the underlying FMR-1 gene mutation, that consists in an increased number of trinucleotide CGG repetitions. Aim: To study families with fragile Xq syndrome, using the Southern technique for the analysis of the mutation. Subjects and methods: Fifteen individuals, pertaining to 6 families with fragile Xq syndrome, were studied. Clinical, cytogenetic and molecular analysis using Southern technique, were done. Results: Five male individuals had a clinically evident syndrome, confirmed by cytogenetic analysis that showed fragility in 10 to 29 percent of studied cells. One subject with a clinical picture suggesting fragile Xq had a normal cytogenetic study. The other studied subjects were the mothers of the five subjects with the syndrome, that must be carriers, and four brothers. Molecular analysis showed that seven subjects (5 males) had a complete mutation, five (4 females) were carriers of a pre mutation and three (2 males) did not have the mutation. Conclusions: The southern technique allows to verify the normal condition of FRAXA locus, identify carriers and to detect complete mutations in fragile Xq syndrome