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Purpose To describe an Italian family in which two separate phenotypes (retinitis pigmentosa and adult onset vitelliform macular dystrophy) are associated with an identical mutation (S212G) in the peripherin/RDS gene. This mutation has already been reported in patients with retinitis pigmentosa, but it has never been previously detected in association with adult onset vitelliform macular dystrophy.Methods A 38-year-old woman complained of bilateral mild metamorphopsias and on ophthalmologic examination she showed the clinical phenotype of adult onset vitelliform macular dystrophy. Her 62-year-old mother was clinically diagnosed with a retinitis pigmentosa, with a severe clinical course.Results In both patients, molecular genetic analysis revealed a 874A→G transition in the exon 2 of the RDS gene leading to the amino acid change of S212G.Conclusions Peripherin/RDS S212G mutation may have damaging effects on the formation and stability of the photoreceptors' disk structure and may be associated with different clinical phenotypes, even in the same family. Intrafamilial phenotypic variability has been reported for other RDS mutations; this supports the possible influence of modifier genes or environmental factors in the clinical expression of RDS gene variants. Moreover, it suggests that in patients with retinal degeneration and peripherin/RDS mutation, caution should be taken both in using molecular genetic results to predict the clinical course of the disease and in offering genetic counseling.

Purpose To report an unusual episode of full-thickness macular hole complicating Stargardt disease with an ABCR mutation.Methods Case report.Results Fundus examination of a 20-year-old healthy man showed typical fundus manifestation with yellowish-round or fish-like flecks associated with vitreous macular adhesion and a round punched-out area in the right eye. Optical coherence tomography (OCT) illustrated a full-thickness macular hole. Molecular genetic examination of the ABCR gene showed two heterozygous missense mutations: R1108C (CGC→TGC) in exon 22 and a splicing mutation IVS6-→1GT – described in the literature in association with Stargardt disease.Conclusions Macular hole was once described in other inherited retinal degenerations (Best disease and Bietti crystalline retinopathy). The pathogenesis gives rise to a host of speculations: widespread alteration of the retinal pigment epithelium; inflammatory mechanisms; a minor trauma which might cause subretinal fibrosis. Surgical procedures were not performed on our patient after his ophthalmologic history and findings were considered.

To determine the toxicological effects of complex mixtures of pesticides, we obtained data on 100 pesticide residues in common food. of central Italy. Fifteen pesticides were more regularly detected at higher levels (dithiocarbamates, benomyllcarbendazim, thiabendazole, diphenylamine, chlorthalonil, procymidone, fenarimol, chlorpropham, vinchlozolin, methidathion, chlorpyriphos-ethyl, parathion-methyl, parathion, chlorfenviphos, pirimiphos-ethyl). Using itemized data on daily food consumption in Italy, we calculated that the average exposure for an adult subject was 716 µg/day, ranging fiom 148 µg of dithiocarbamates to 1 pg of pirimiphos-ethyl. We made a mixture of these 15 pesticides at concentrations proportional to the ratio determined in foods and tested it with the Salmonellamicrosome assay, with and without metabolic activation with PCB-induced rat liver S9. No mutagenic activity was observed at concentrations up to 500 µg/plate. We also tested the same mixture at concentrations ranging from 0.1 to 20 µg/ml on human lymphocytes in vitro, and observed a slight but statistically significant increase in sister-chromatid exchanges at 1 µg/ml. We also administered the mixture in corn oil by gavage to Wistar rats at doses of 1, 10, and 100 µg/kg. After 24 hr the ratio between bone marrowpolychromatic and normochromatic lymphocytes (a sign of cellular toxicity) was decreased by the exposure, but we did not observe a significant increase in the frequency of micronuclei. We conclude that thepesticide mixture did not have appreciablegenotoxic activity in the assays used.

Earlier analysis of the Italian population showed patterns of genetic differentiation that were interpreted as being the result of population settlements going back to pre-Roman times. DNA disease mutations may be a powerful tool in further testing this hypothesis since the analysis of diseased individuals can detect variants too rare to be resolved in normal individuals. We present data on the relative frequencies of 60 cystic fibrosis (CF) mutations in Italy and the geographical distribution of the 12 most frequent CF mutations screened in 3492 CF chromosomes originating in 13 Italian regions. The 12 most frequent mutations characterize about 73% of the Italian CF chromosomes. The most common mutation, ΔF508, has an average frequency of 51%, followed by N1303K and G542X, both with average frequencies around 5%. Multivariate analyses show that the relative frequencies of CF mutations are heterogeneous among Italian regions, and that this heterogeneity is weakly correlated with the geographical pattern of non-DNA 'classical' genetic markers. The northern regions are well differentiated from the central-southern regions and within the former group the western and eastern regions are remarkably distinct. Moreover, Sardinia shows the presence of mutation T338I, which seems absent in any other European CF chromosome. The north-western regions of Italy, characterized by the mutation 1717-1G→A, were under Celtic influence, while the north-east regions, characterized by the mutations R1162X, 2183AA→G and 711 + 5G→A, were under the influence of the Venetic culture.