HHV-8 prevalence, immunosuppression and Kaposi's sarcoma in South Italy.

The identification of HHV-8 has opened the way for numerous epidemiological studies aimed at determining both the prevalence of HHV-8 in various sub-groups of the population (affected or not by KS) and at identifying possible cofactors necessary for the development of KS. We set up a study to evaluate the prevalence of HHV-8 in the South of Italy in KS cases, hospital patients and blood donors and to verify the role of immunosuppression in KS. In KS patients the prevalence of lytic and latent antigens were both 91% (29 positive cases). Lytic and latent antigens have prevalence rates of 20% and 15% respectively in hospital patients. In the donor group the rates were 16% for lytic antigens and 2% for latent antigens. The most recurrent chronic pathology in KS patients was cardiopathy (5 cases). The pathological case histories report 4 cases of Herpes Zoster, 6 of diabetes, one case of hepatitis C who had also had gonorrea. There was also a case, negative to HHV-8, who had had malaria after residing for three years in Oristano in Sardinia (a zone with high endemic malaria). Our study confirms that in Southern Italy there are relatively high prevalences of HHV-8 both in the general population and in blood donors and that immunodysregulation may be involved in the pathogenesis of KS. Other studies are necessary to confirm the sexual transmission of the HHV-8 virus and to better understand the natural history of HHV-8 infection.

HCV and hepatocellular carcinoma: A case-control study in an area of hyperendemicity.

HCV is an RNA virus that cannot be integrated with the host genome; it can, however, exert its oncogenetic potential indirectly by contributing to the modulator effects of the host immune system probably through a capacity to escape the immune system. We have carried out a case controlled study in a hyperendemic area on HCV infection and liver cancer. We screened 114 liver cancer and 226 controls. All patients were at first diagnosis and examined. For liver cancer the risk was (OR=32.9, 95% CI 16.5-65.4, p<0.0001). Our study is particularly important for public health since it shows that in the South of Italy, because of the high prevalence of HCV and the high life expectancy, there are good reasons to suppose that the incidence rate of liver cancer will continue to increase in the next few years.

Sequence-based exon prediction around the synaptophysin locus reveals a gene-rich area containing novel genes in human proximal Xp.

The human Xp11.23-p11.22 interval has been implicated in several inherited diseases including Wiskott-Aldrich syndrome; three forms of X-linked hypercalciuric nephrolithiaisis; and the eye disorders retinitis pigmentosa 2, congenital stationary night blindness, and Aland Island eye disease. In constructing YAC contigs spanning Xp11. 23-p11.22, we have previously shown that the region around the synaptophysin (SYP) gene is refractory to cloning in YACs, but highly stable in cosmids. Preliminary analysis of the latter suggested that this might reflect a high density of coding sequences and we therefore undertook the complete sequencing of a SYP-containing cosmid. Sequence data were extensively analyzed using computer programs such as CENSOR (to mask repeats), BLAST (for homology searches), and GRAIL and GENE-ID (to predict exons). This revealed the presence of 29 putative exons, organized into three genes, in addition to the 7 exons of the complete SYP coding region, all mapping within a 44-kb interval. Two genes are novel, one (CACNA1F) showing high homology to alpha1 subunits of calcium channels, the other (LMO6) encoding a product with significant similarity to LIM-domain proteins. RT-PCR and Northern blot studies confirmed that these loci are indeed transcribed. The third locus is the previously described, but not previously localized, A4 differentiation-dependent gene. Given that the intron-exon boundaries predicted by the analysis are consistent with previous information where available, we have been able to suggest the genomic organization of the novel genes with some confidence. The region has an elevated GC content (>53%), and we identified CpG islands associated with the 5' ends of SYP, A4, and LMO6. The order of loci was Xpter-A4-LMO6-SYP-CACNA1F-Xcen, with intergenic distances ranging from approximately 300 bp to approximately 5 kb. The density of transcribed sequences in this area (>80%) is comparable to that found in the highly gene-rich chromosomal band Xq28. Further studies may aid our understanding of the long-range organization surrounding such gene-enriched regions.

Compound heterozygosity for Hb Lepore-Boston and Hb Neapolis (Dhonburi) [beta 126(H4)Val-->Gly] in a patient from Naples, Italy.

The simultaneous presence of two hemoglobin variants has been detected in a 14-month-old patient affected by thalassemia intermedia. The two variants were characterized by a combination of allele-specific amplification methods and mass spectrometric procedures carried out on isolated globins. These were identified as Hb Lepore-Boston and Hb Neapolis (also known as Hb Dhonburi) or beta 126 (H4)Val-->Gly. Hb Lepore-Boston is the most common hybrid variant detected in Campania and several cases of Hb Neapolis which causes a mild hypochromic microcytic anemia have been identified in this region in the last few years. This is the first report of a double heterozygosity involving Hb Lepore-Boston and Hb Neapolis.

Hb O-Arab [beta 121(GH4)Glu-->Lys]: association with DNA polymorphisms of African ancestry in two Mediterranean families.

Hb O-Arab [beta 121(GH4)Glu-->Lys] was detected in two Mediterranean families, one from Southern Italy and the other from Albania. The GAA-->AAA mutation at codon 121 was characterized by DNA sequencing. The mutant genes were associated with the same beta-globin gene framework variant and with the rare Hpa I/3' beta polymorphic restriction site generating a 7.0 kb fragment. However, at 5' the gene of the Italian family was associated with the restriction fragment length polymorphism subhaplotype [+ - - - +] and the Taq I/3'G gamma polymorphic site, while that of the Albanian family was associated with subhaplotype [- - - - +] but not with the Taq I/3'G gamma site. The particular features of these polymorphisms support the hypothesis of an African origin for the Hb O-Arab gene and a subsequent recombination event leading to the haplotype found in the Italian family.