Epilepsy in Sardinia, insular Italy: a population-based prevalence study.

BACKGROUND: Sardinia, insular Italy, represents a particular epidemiological setting to investigate polyfactorial diseases, by virtue of its phylogeny and geographic isolation over time and of a well-established network of health operators and information systems. We present the first prevalence study of epilepsy conducted on a large Sardinian population by means of multiple source ascertainment. METHODS: Cases were ascertained in the province of Sassari (population of 333,576) for the period between January 1, 2000 and December 31, 2008 based on records from (a) the District Center for Epilepsy, (b) the District Health Information System Unit, and (c) the neurologists practicing within the National Health System. RESULTS: The total crude prevalence of active epilepsy on December 31, 2007 was 6.62 per 1,000 (95% CI 5.3-7.9), 6.51 in men (95% CI 5.4-7.6), and 6.73 in women (95% CI 5.7-7.7). The highest prevalence (8.78 per 1,000) was estimated in the elderly (≥65 years). 50.5% were symptomatic epilepsies. Of these, over 50% were secondary to cerebrovascular disorders in the elderly. CONCLUSIONS: The epidemiological behavior of prevalence of active epilepsy in Sardinia appears to be in line with that of other developed countries, despite the role that population-specific genetic and environmental factors exert in modulating the risk for other neurological diseases. The action of (exogenous) factors commonly distributed in western populations, also influencing, at least partially, the epidemiological patterns of epilepsy in Sardinians, should not be ruled out.

Fetal HLA typing in beta thalassaemia: implications for haemopoietic stem-cell transplantation.

Stem-cell transplantation can cure beta thalassaemia. We aimed to assess whether fetal HLA typing done early in the pregnancy of couples who were at risk of beta thalassaemia could provide an alternative to pregnancy termination if the prospect of a bone-marrow transplantation from a family member was available. In our clinic in Sardinia, we did fetal HLA typing for 49 couples at risk of having a baby with beta thalassaemia. Two affected children were born and successfully received a transplantation from a family donor. Five non-affected fetuses were HLA compatible with an affected sibling and their cord blood was harvested for a future transplantation.

Amyotrophic lateral sclerosis in Sardinia, insular Italy, 1995-2009.

Recent genetic studies suggest a Sardinian type of amyotrophic lateral sclerosis (ALS). Thus, ALS incidence, prevalence and survival were investigated in a large population of Sardinians aimed to disclose population-specific patterns and their temporal changes. This is a population-based incidence and prevalence study in northern and central Sardinia, insular Italy (over 700,000 population). Incidence rates were computed for the time interval 1995-2009 and by quinquennia. Prevalence was computed for prevalence days 31 December 2004 and 2009. Onset-based survival for 1995-2009 is also reported. All ALS patients (El Escorial Criteria) in the study area were retrospectively included. The ALS crude incidence from 2005-2009 was 2.5 (95 % CIs: 0.1, 4.9), 3.4 in men and 1.6 in women. Onset occurred most often between the age of 65-74 years in men and 55-64 years in women. The ALS incidence tended to increase over the period 1995-2009. The mean age at onset was 61.7 years with no difference based on gender, varying significantly from 59.9 years in 1995-1999 to 63.9 years in 2005-2009. On December 31, 2009, the ALS crude prevalence was 10.8 per 100,000 (95 % CIs: 8.6, 13.1), 13.8 in men and 8.0 in women, whereas it was 6.3 per 100,000 (95 % CIs: 4.1, 8.6) on December 31, 2004 (M:F ratio of 0.95). Mean survival from onset was 37.0 months, with no difference based on gender, and a tendency to decrease during the period 1995-2009, in relation to type and age of onset. The population-based incidence and prevalence data of ALS in Sardinians indicate an increase of the disease occurrence over the past 40 years, providing support for a population-specific variant of ALS in Sardinia.

Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene.

OBJECTIVE: To perform an extensive screening for mutations of amyotrophic lateral sclerosis (ALS)-related genes in a consecutive cohort of Sardinian patients, a genetic isolate phylogenically distinct from other European populations. DESIGN: Population-based, prospective cohort study. PATIENTS: A total of 135 Sardinian patients with ALS and 156 healthy control subjects of Sardinian origin who were age- and sex-matched to patients. INTERVENTION: Patients underwent mutational analysis for SOD1, FUS, and TARDBP. RESULTS: Mutational screening of the entire cohort found that 39 patients (28.7%) carried the c.1144G>A (p.A382T) missense mutation of the TARDBP gene. Of these, 15 had familial ALS (belonging to 10 distinct pedigrees) and 24 had apparently sporadic ALS. None of the 156 age-, sex-, and ethnicity-matched controls carried the pathogenic variant. Genotype data obtained for 5 ALS cases carrying the p.A382T mutation found that they shared a 94-single-nucleotide polymorphism risk haplotype that spanned 663 Kb across the TARDBP locus on chromosome 1p36.22. Three patients with ALS who carry the p.A382T mutation developed extrapyramidal symptoms several years after their initial presentation with motor weakness. CONCLUSIONS: The TARDBP p.A382T missense mutation accounts for approximately one-third of all ALS cases in this island population. These patients share a large risk haplotype across the TARDBP locus, indicating that they have a common ancestor.

Clustering of multiple sclerosis, age of onset and gender in Sardinia.

In diseases with unpredictably long latent period, such as multiple sclerosis (MS), cluster studies, and the analysis of disease distribution by gender and age of onset, can provide clues to disease etiopathogenesis. Sardinia, insular Italy, is among the regions at highest risk for MS worldwide. Multiple epidemiological evidences favour the role of exogenous factors in modulating MS incidence in Sardinians. Its steady increase over time is the main determinant for the observed increased prevalence of MS. Incidence is especially increasing for MS with RR initial course, in individuals with older age and in the female population. More women that will develop MS are believed to being born now. Early childhood is likely the age of susceptibility to MS, and especially in women, in most recent cases, and in individuals developing MS at earlier age and with RR initial clinical course. These evidences suggest that specific exogenous (gender-related? perinatal?) factors have recently been exerting as determinants of the MS increase in Sardinians and the change of its phenotype. Such factors are unlikely agents with fixed latency incubation period, but they could rather be the result of recent lifestyle changes and/or of their interplay with a highly susceptible genetic background.