Autosomal dominant Brody disease cosegregates with a chromosomal (2;7)(p11.2;p12.1) translocation in an Italian family

Brody disease is a rare muscle disorder characterized by exercise-induced impairment in muscle relaxation, due to a markedly reduced influx of calcium ions in the sarcoplasmic reticulum. A subset of autosomal recessive families harbour mutations in the ATP2A1 gene, encoding the fast-twitch skeletal muscle sarcoplasmic reticulum Ca(2+) ATPase (SERCA1). Rare autosomal dominant families have been described, in which ATP2A1 was excluded as the causative gene, further supporting genetic heterogeneity. We report four individuals from a three-generation Italian family with a clinical phenotype of Brody disease, in which linkage analysis excluded ATP2A1 as the responsible gene. The disease cosegregates in an autosomal dominant fashion with an apparently balanced constitutional chromosome translocation (2;7)(p11.2;p12.1), suggesting a causal relationship between the rearrangement and the phenotype. FISH analysis using YAC and PAC clones as probes refined the breakpoint regions to genomic segments of about 164 and 120 kb, respectively, providing a possible clue to pinpoint the location of a novel gene responsible for this rare muscle disorder.     

Epidemiology of tuberculosis in immigrant patients hospitalised in Infectious Diseases Units in Italy: multicentric study

In order to retrospectively evaluate the prevalence of immigrant patients affected by active tuberculosis, we analysed the clinical data of 2255 immigrant patients hospitalised during 2002 in ordinary admission or in Day Hospital in 48 Clinics of Infectious Diseases. In all, 303 patients were affected by active tuberculosis (13.4% of the total immigrant hospitalised patients); 30 patients (9.9%) were also HIV-positive. There was a considerable male gender bias (62.5%); the mean age was 29.7 years; 144 patients were from Africa (47.5%), 72 (23.7%) from Asia, 47 (15.5%) from eastern Europe and 40 (13.2%) from South America. The clinical variants were: pulmonary (57.7%), lymph node (15.8%), meningitis (13.8%), intestinal (4.2%), bone (3.3%), pleurical (2.3%), peritoneal (2.3%) and renal (0.6%). We conclude that tuberculosis is a very frequent disease among immigrants, especially of African origin. The high percentage is due to several factors, such as no vaccine prophylaxis and poor, overcrowded living conditions. It is fundamental to focus on the need to provide better health support for all subjects by setting up screening plans to estimate the real incidence of this pathology and ensure medical treatment to prevent the spread of this infection among immigrants and the local host population.     

Central precocious puberty and abnormal chromosomal patterns

Central precocious puberty (PP) can be caused by chromosomal aberrations. We report three patients presenting with central PP in whom karyotype analysis demonstrated abnormal chromosomal patterns. The first patient was affected by the triple-X syndrome, commonly characterized by premature ovarian failure. The second patient, a girl with inv dup(15)(pter→q12::q12→pter), had a chromosomal aberration involving an imprinted region of the human genome, whose deletion is commonly associated with Prader-Willi syndrome (PWS) and hypogonadotrophic hypogonadism. The third patient was a boy carrying a rare chromosome abnormality, the duplication of chromosome 9 (q22→qter). All patients had mental retardation, which was mild in patient 1, moderate in patient 2, and severe in case 3. They underwent treatment with luteinizing hormone releasing hormone (LHRH) analogs, which were able to stop the progression of the sexual development. We confirm that chromosomal aberrations are an important cause of central PP, and that karyotype analysis in patients with PP and mental retardation, even if mild, is necessary because chromosomal abnormalities can be present.     

Human gene for proliferating cell nuclear antigen has pseudogenes and localizes to chromosome 20

We have isolated from a human genomic library a pseudogene of the proliferating cell nuclear antigen (PCNA)gene. Its sequence shows a 78% similarity with the human PCNA/cDNA. The PCNAgene is located on human chromosome 20, while the pseudogene maps to chromosome region XpterXq13. An additional locus detected by the full-length PCNA cDNA, but not by intron probes, segregates concordantly with chromosome region 6p126pter and probably represents a second pseudogene.     

Craniofacial dyssynostosis: case report and review

Craniofacial dyssynostosis (CFD) is a rare disorder related to premature closure of the lambdoid suture and the posterior part of the sagittal suture. Epilepsy, mental retardation, abnormalities of the corpus callosum, and short stature have been reported. We studied a patient with CFD, hydronephrosis, and partially empty sella turcica; the latter two features are reported for the first time. We discuss the brain anomalies and their neurologic sequelae, which are part of the CFD phenotype.     

Reciprocal stimulation of gammadelta T cells and dendritic cells during the anti-mycobacterial immune response

Gammadelta T cells and dendritic cells (DC) are two distinct cell types of innate immunity that participate in early phases of immune response against Mycobacterium tuberculosis infection. Here we show that a close functional relationship exists between these cell populations. Using an in vitro coculture system, Vgamma1 T cells from Tcrb(-/- )mice were found to be activated by DC infected in vitro with BCG, as indicated by the elevated CD69 expression, IFN-gamma secretion and cytotoxic activity. This activation process was due to a non-cognate mechanism since it required neither cell to cell contact nor interaction between the TCR and a specific antigen, but was mediated by DC-derived IL-12. Reciprocally, Vgamma1 T cells provided a key cytokine, IFN-gamma, which increased IL-12 production by BCG-infected DC. Moreover, exposure of BCG-infected DC to Vgamma1 T cells conditioned the former to prime a significantly stronger anti-mycobacterial CD8 T cell response. Consequently, stimulation of gammadelta T cells and their non-cognate interaction with DC could be applied as an immune adjuvant strategy to optimize vaccine-induced CD8 T cell immunity.     

Efficacy of human recombinant erythropoietin plus IFN-alpha in patients affected by chronic hepatitis C.

Determination of serum iron levels in patients affected by chronic hepatitis C is considered fundamental for studying the response to interferon-alpha (IFN-alpha) treatment. IFN could induce anemia, which is promptly corrected by exogenous administration of recombinant human erythropoietin (rHuEPO). The aim of our study was to verify the possible beneficial effect of rHuEPO in patients affected by chronic hepatitis C and treated with IFN. Seventy consecutive patients (42 males and 28 females, mean age 46.4+/-5.2 years) affected by chronic hepatitis C were enrolled. In all patients, chronic hepatitis C was diagnosed on the basis of clinical and biological findings (alanine aminotransferase [ALT] serum levels at least 2-fold higher than normal values for at least 12 months and the presence of anti-HCV antibodies). All patients were negative for hepatitis B virus (HBV) infection, hepatitis D virus (HDV infection, and HIV infection. Statistical analysis was carried out using the Wilcoxon nonparametric sum rank test, the Spearman correlation rank test, and the Friedman ANOVA and Kendall coefficient of concordance. At the end of the treatment, our study series showed significant differences in serum levels of AST (p < 0.001), iron (p < 0.001), and ferritin (p < 0.001). At the end of the follow-up period, significant differences were seen in ALT, aspartate (AST), and iron ferritin and transferrin levels. All differences favored patients who received IFN-alpha and rHuEPO. We think that the depletion of circulating iron may improve the immune response impaired by iron accumulation in the liver. Our study confirms the important role played by iron in the response to IFN treatment, suggesting that the use of rHuEPO induces a better response to IFN in patients with chronic hepatitis C by activation of erythropoiesis.     

Heterogeneity in intergenic regions of the ribosomal repeat of the pine-blister rustsCronartium flaccidum andPeridermium pini

Mixed aeciospore isolates ofCronartium flaccidum andPeridermium pini were obtained from single-tree infections in Britain, Italy and Greece. The 5.8s ribosomal RNA gene and flanking intergenic transcribed spacer regions ITS 1 and ITS2 were found to be highly similar betweenC. flaccidum andP. pini. Within samples heterogeneity was detected at three nucleotide loci in the ITS1 and at four loci in the ITS2 suggesting that several fungal genotypes may occur at a single infection court. The heterogeneity was confirmed by heteroduplex polymorphism analysis of mixed aeciospore products. RFLP of the ribosomal intergenic spacer region 1 (IGSI) amplified from the same templates indicated limited sequence polymorphism in some copies of this repeated locus. Both the sexual and asexual forms ofC. flaccidum show evidence of sequence polymorphism in two independent, non-coding regions of the ribosomal gene array. Variation appears to be greater in the sexual formC. flaccidum, than in the monoaecious formP. pini.