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Objective. A recent study illustrated that a functional polymorphism in the prodynorphin (PDYN) gene promoter encoding the dynorphin opioid peptide is a significant risk factor for temporal lobe epilepsy (TLE). Here we wished to better address the role of the PDYN gene in the genetic predisposition to TLE. Methods. We tested the distribution of the PDYN genotypes (H/H, H/L,L/L) and alleles (H,L) in 143 patients (79 females and 64 males; mean age 0 49,2 ± 18.1 years) with non-lesional TLE and 259 age and sex-matched normal individuals. In all patients, the diagnosis of non-lesional TLE was based on comprehensive clinical, neuropsychological, electroencephalographic, and routine magnetic resonance evaluations. Fifty-two/143 (36.4%) patients had a family history of seizures or febrile convulsions in one or more first -to third-degree relatives. The mean age at seizure onset was 31.2 years with a range of 0.5 to 83 years.Results We found that PDYN promotor low-expression L-alleles confer, in a recessive manner; a slight increased risk for TLE in patients with a family history for seizures. Most important, association between PDYN polymorphism and TLE was highly significant in females but not formally significant in males.

We have carried out a systematic study of the molecular basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency on a sample of 53 male subjects from Calabria, in southern Italy. Our sequential approach consisted of the following steps: (1) Partial biochemical characterization was used to pinpoint candidate known variants. The identity of these was then verified by restriction-enzyme or allele-specific oligonucleotide hybridization analysis of the appropriate PCR-amplified fragment. (2) On samples for which there was no obvious candidate mutation, we proceeded to amplify the entire coding region in eight fragments, followed by single-strand conformation polymorphism (SSCP) analysis of each fragment. (3) The next step was M13 phage cloning and sequencing of those individual fragments that were found to be abnormal by SSCP. Through this approach we have identified the molecular lesion in 51 of the 53 samples. In these we found a total of nine different G6PD-deficient variants, five of which (G6PD Mediterranean, G6PD A-, G6PD Coimbra, G6PD Seattle, and G6PD Montalbano) were already known, whereas four are new (G6PD Cassano, G6PD Cosenza, G6PD Sibari, and G6PD Maewo). G6PD Mediterranean is the commonest variant, followed by G6PD Seattle. At least seven of the variants are present, at polymorphic frequencies, in the Calabria region, and some have a nonrandom distribution within the region. This study shows that the genetic heterogeneity of G6PD deficiency in Calabria, when analyzed at the DNA level, is even greater than had been anticipated from biochemical characterization. The sequential approach that we have followed is fast and efficient and could be applied to other populations.

We have carried out a systematic study of the molecular basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency on a sample of 53 male subjects from Calabria, in southern Italy. Our sequential approach consisted of the following steps: (1) Partial biochemical characterization was used to pinpoint candidate known variants. The identity of these was then verified by restriction-enzyme or allele-specific oligonucleotide hybridization analysis of the appropriate PCR-amplified fragment. (2) On samples for which there was no obvious candidate mutation, we proceeded to amplify the entire coding region in eight fragments, followed by single-strand conformation polymorphism (SSCP) analysis of each fragment. (3) The next step was M13 phage cloning and sequencing of those individual fragments that were found to be abnormal by SSCP. Through this approach we have identified the molecular lesion in 51 of the 53 samples. In these we found a total of nine different G6PD-deficient variants, five of which (G6PD Mediterranean, G6PD A-, G6PD Coimbra, G6PD Seattle, and G6PD Montalbano) were already known, whereas four are new (G6PD Cassano, G6PD Cosenza, G6PD Sibari, and G6PD Maewo). G6PD Mediterranean is the commonest variant, followed by G6PD Seattle. At least seven of the variants are present, at polymorphic frequencies, in the Calabria region, and some have a nonrandom distribution within the region. This study shows that the genetic heterogeneity of G6PD deficiency in Calabria, when analyzed at the DNA level, is even greater than had been anticipated from biochemical characterization. The sequential approach that we have followed is fast and efficient and could be applied to other populations.

35,660 healthy children attending secondary school in the Cosenza province, in the North of Calabria (Southern Italy), were screened for G6PD deficiency. Of 16,787 schoolboys, 209 were found to be G6PD deficient (1.24%). Of these, 99 (47.37%) had red cell G6PD activity below 5%, and they were classified as having the G6PD Mediterranean phenotype. The remaining 110 (52.63%), had a mild to moderate degree of deficiency, with an enzyme activity between 5 and 60%. Of these, 82 (74.55%) were electrophoretically normal, while 17 (15.45%) were electrophoretically fast and 11 (10.0%) were electrophoretically slow. The highest incidence of G6PD deficiency is on the Ionian Coast and along the Crati and Esaro river valleys, in good agreement with the distribution of the past malarial endemicity.

Several pathogenetic factors seem to contribute to the development of Alzheimer's disease (AD). Some data point to a role for traumatic brain injury (TBI), but this suggestion is not universally supported. Mayeux et al. have shown that TBI increases the risk of AD, but only through a synergistic relationship with apolipoprotein epsilon (Apo E) 4. We present the results of a cross-sectional and longitudinal study of the relationship between these factors, conducted in northern and southern Italy. We studied 337 consecutive patients with probable AD and 63 subjects with mild cognitive impairment (MCI). Information concerning head injuries was collected by interview of informants and review of medical records. Twenty-one patients with AD and 9 with MCI were found to have a history of TBI with loss of consciousness. AD and MCI patients with a history of TBI, compared with control groups matched for age, sex, education and degree of mental impairment, showed more marked depressive and behavioural disturbances (Global Deterioration Scale and Neuropsychiatric Inventory, p

Estrogen receptor 1 gene polymorphisms (ESR1) have been found to be associated with multiple sclerosis (MS) in both Japanese and Finnish populations. We investigated the association between ESR1 polymorphisms (PvuII and XbaI) and MS in a study of 132 MS patients and 129 controls from the same geographic background (southern Italy). Allelic and genotypic frequencies were not different between MS patients and population controls for either the PvuII or XbaI polymorphism. This result suggests that the association between a given disease and a genomic characteristic must be confirmed by separate investigations in different populations. © 2002 Elsevier Science Ireland Ltd. All rights reserved.