Cardiac sympathetic denervation precedes nigrostriatal loss in the E46K mutation of the alpha-synuclein gene (SNCA).

INTRODUCTION: Here we report the case of an asymptomatic carrier of the E46K substitution in alpha-synuclein gene where we have documented that cardiac sympathetic denervation precedes nigrostriatal dopaminergic loss. MATERIAL AND METHODS: She has been followed up regularly with standard neurological examination, UPDRS, neuropsychological formal testing, parkinson disease sleep scale-PDSS, Epworth scale, Hamilton-D scale, SCOPA Aut, orthostatic hypotension test, brief smell identification test, polysomnography, cerebral 123-I-FP-CIT SPECT, and, 123I-MIBG cardiac scintigraphy. RESULTS: She shows no presence of orthostatic hypotension. Olfactory test results demonstrate normal limits. In the PSG the nocturnal sleep shows mild abnormalities although the sleep efficiency and stage proportion remain under normal limits. The 123-I-FP-CIT SPECT is normal; in contrast, the 123I-MIBG cardiac scintigraphy shows a complete lack of isotopic uptake compatible with a severe sympathetic myocardial denervation. CONCLUSION: This example of monogenic autosomal dominant parkinsonism due to an alpha-synuclein mutation favours the hypothesis that peripheral autonomous nervous system involvement occurs earlier than the CNS degeneration.

Use of cytological specimens for p53 gene alteration detection in oral squamous cell carcinoma risk patients.

AIMS: Recurrence and multifocal nature are two important characteristics of oral squamous cell carcinoma. Leukoplakia is the most frequent pre-cancerous oral lesion and, in most cases, it is not possible to predict malignant capacity. The objective of this study is to identify p53 alterations in cells taken from the oral cavity of at-risk patients. MATERIALS AND METHODS: The following samples were collected from 34 patients with oral leukoplakia with and without previous carcinoma: oral rinse, a brush swabbed over the lesions and hair roots. Mutational analysis of the p53 gene was performed by single-strand conformation polymorphisms and confirmed by DNA sequencing. RESULTS: We detected 11 mutations in p53 gene in oral cytological specimens. These alterations were observed only in brush cytology samples in patients without previous carcinoma, and in both samples (rinse and brush) in patients with previous carcinoma. Three of these patients had disease recurrence. CONCLUSION: This non-invasive technique may be useful in the follow-up of at-risk patients, and introduces new possibilities to analyse molecular markers before malignant lesions are clinically apparent.

X-linked microsatellites in two Northern Spain populations.

The X-chromosomal microsatellites HPRTB, DXS101, ARA, DXS7423, and DXS8377 were analysed by a pentaplex PCR in an expanded population sample from Cantabria and an independent sample of unrelated individuals from the Basque Country. Allele frequencies showed similar distributions, but minor variations were found for some loci.

Y-chromosomal STR haplotype diversity in males from Santa Catarina, Brazil.

One-hundred and nine unrelated and healthy males from Santa Catarina, Brazil were included in this study. Allele frequencies and gene diversities for the loci DYS456, DYS458 and DYS448 were calculated. A comparison between our population and others was performed.

DNA typing of Diptera collected from human corpses in Portugal.

Medico-legal entomology, one area in the broad field of entomology, is routinely used in forensic applications. Insects are often collected from a corpse during criminal information related to the body, but requires the fast and accurate identification of the species attracted to the remains. The local entomofauna in most cases is important for explaining entomological evidence. The survey of the local entomofauna has become a fundamental first step in forensic entomological studies, because different geographical distributions, seasonal and environmental factors may influence the decomposition process and the occurrence of different species on corpses. A morphological and DNA-based methods for species identification were used in this study. Thirty-two cases are reported from indoors and outdoors conditions. Specimens were collected from corpses during autopsy procedures in the National Institute of Legal Medicine, Portugal, and cases were summarized by sex, death local, month of discovery, probable cause of death, species found and number of analyzed specimens. Just eight species, mainly Calliphoridae together with one Sarcophagidae were reported from corpses. The DNA sequencing was performed to study the mitochondrial encoded subunit I of the cytochrome oxidase gene. The aim of this work was the beginning of a database of the cadaveric entomofauna in Portugal.

A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease.

BACKGROUND: Frontotemporal dementia with parkinsonism is often linked to chromosome 17 and is related to mutations in the MAPT gene. In some families the genetic basis is still unknown. The authors report two pedigrees with FTDP-17 harboring a novel mutation (K317M) in exon 11 in the MAPT gene. METHODS: The authors identified two apparently unrelated pedigrees with an autosomal dominant neurodegenerative condition. Thirteen patients were examined and eight autopsies were performed. RESULTS: Mean age at onset was 48 years. Mean disease duration was 6 years. Dysarthria often heralded the disease. All cases had parkinsonism and pyramidalism and half of them had amyotrophy. Behavioral or personality changes were not a prominent feature. Cognitive decline appeared late in the evolution. Neuropathologically, a massive degeneration of the substantia nigra without Lewy bodies was a constant finding. A variable degree of frontotemporal atrophy was found. Corticospinal tract degeneration and anterior horn neuron loss were present in six of seven autopsies in which the spinal cord was examined. An extensive deposition of abnormal tau protein in a mixed pattern (neuronal, glial) was observed. Pick's bodies were not seen. Biochemical analysis of tau revealed two bands of 64 and 68 kDa. CONCLUSION: Genetic analysis revealed the same novel mutation (K317M) in exon 11 of the MAPT gene in both pedigrees. A common haplotype between members of the two pedigrees suggests that they belong to the same family.