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Migraine is a debilitating disorder affecting a large proportion of the population. The effect of methylenetrathydrofolate reductase (GeneID: 4524) polymorphisms in migraine etiology and development has been a theme of great interest. Several populations were evaluated with contradictory results. In this case-control study, we investigated the effect of the C677T polymorphism in MTHFR, as a genetic risk factor for migraine, in the Portuguese population. We observed that, overall, there was no significant difference in the frequencies of MTHFR C677T genotypes or of the T-allele among the Portuguese migraineurs when compared to controls. There was also no association of migraine with aura with MTHFR genotypes or with the T-allele, in contrast with previous studies. Regarding the risk of the T-allele homozygote carriers, there was an equal probability to develop migraine with aura over migraine without aura in our patients. Thus, we conclude that the C677T MTHFR polymorphism, responsible for a reduction of the MTHFR activity in folate metabolism, is not a major genetic susceptibility factor for migraine in the Portuguese population. [ABSTRACT FROM AUTHOR]

Benign hereditary chorea (BHC) is an autosomaldominant disorder of early onset characterized by a slowly progressing or nonprogressing chorea, without cognitive decline or other progressive neurologic dysfunction, but also by the existence of heterogeneity of the clinical presentation within and among families. The genetic cause of BHC is the presence of either point mutations or deletions in the thyroid transcription factor 1 gene ( TITF1). We studied a Portuguese BHC family composed of two probands: a mother and her only son. The patients were identified in a neurology out-patient clinic showing mainly involuntary choreiform movements since childhood, myoclonic jerks, falls, and dysarthria. We performed magnetic resonance imaging (MRI), electroencephalogram (EEG), nerve conduction studies, thyroid ultrasound scan, biochemical thyroid tests, and electrocardiogram (ECG). We excluded Huntington disease by appropriate genetic testing and sequenced the entire TITF1 gene for both patients. The patients showed MRI alterations: (1) in the mother, abnormal hyperintense pallida and cortical cerebral/cerebellar atrophy; and (2) in the son, small hyperintense foci in the cerebellum and subtle enlargement of the fourth ventricle. Sequence analysis of the TITF1 gene in these patients revealed the presence of a heterozygous C > T substitution at nucleotide 745, leading to the replacement of a glutamine at position 249 for a premature stop codon. A previously undescribed nonsense mutation in the TITF1 gene was identified as being the genetic cause of BHC in this family. [ABSTRACT FROM AUTHOR]

Context: Machado-Joseph disease (MJD), an autosomal dominant spinocerebellar degeneration caused by an expanded CAG repeat on chromosome 14q32.1, is a heterogeneous disorder for clinical manifestations. The reasons for the wide range of neurologic findings in this disease are poorly understood. Objective: To explain part of this heterogeneity through the association of the neurologic findings with sex, disease duration, age of onset, clinical type, and size of CAG repeat expansion. Design: A case-control study. Setting: Ambulatory care. Patients: A consecutive sample of 62 patients with MJD. Main Outcome Measure: Neurologic signs. Results: A direct relationship was found between the disease duration and severity of gait and limb ataxia, dysarthria, dysphagia, fasciculations, pyramidal syndrome, and ophthalmoplegia (P<.02). The most severe forms of nuclear ophthalmoplegia were associated with type 1 MJD, whereas those of supranuclear ophthalmoplegia were associated with type 3 MJD (P<.001). It was also found that higher mean (CAG)[sub n] lengths were associated with worse degrees of the pyramidal syndrome and dystonia (P<.001). The presence and severity of nystagmus, eyelid retraction, rigidity and/or bradykinesia, and optic atrophy were not clearly associated with any of the predictive variables under study. Conclusions: Disease duration can explain part of the heterogeneity of ataxia, dysarthria, dysphagia, fasciculations, pyramidal syndrome, and ophthalmoplegia, in MJD. Type 1 MJD was positively associated with nuclear ophthalmoplegia; type 3 MJD was positively associated with supranuclear ophthalmoplegia. Higher mean CAG lengths were found to correlate with the pyramidal syndrome and dystonia. Nystagmus, eyelid retraction, rigidity and/or bradykinesia, and optic atrophy were hardly attributable to any known reason or variable. [ABSTRACT FROM AUTHOR]