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Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiovascular disorder worldwide. It is the leading cause of sudden cardiac-related death in young people and a major cause of cardiac failure and death in elderly people. However, HCM frequently goes undiagnosed until the appearance of overt signs and symptoms, thereby delaying prophylactic and therapeutic measures. We screened patients for sarcomeric genes associated with HCM to obtain information that could be useful for an early diagnosis and so limit the severe consequences of silent HCM. We recruited 39 families with HCM from southern Italy and found mutations in 41% of families (12 with familial HCM and 4 with sporadic HCM). The remaining 23 families (59%) were negative for myofilament gene mutations. Of the 12 mutations identified, 8 were novel. Screening of the other family members available revealed that 27 had mutations; 11 of these individuals had no signs or symptoms suggestive of HCM. This study, besides characterizing the spectrum of mutations in another childhood population, and revealing an even greater genetic heterogeneity than formerly recognized, may increase genotype-phenotype correlations, and thus may help to identify asymptomatic candidates for early preventive or therapeutic measures. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the complement factor H (CFH) p.402Y>H polymorphism as a risk factor in age related macular degeneration (AMD) in an Italian population. Methods: 104 unrelated Italian AMD patients and 131 unrelated controls were screened for the CFH polymorphism p.402Y>H (c.1277 T>C), which has been associated with AMD. Retinography was obtained for patients and controls; the AMD diagnosis was confirmed by fluorescein angiograms. The c.1277 T>C polymorphism was genotyped with the TaqMan real time polymerase chain reaction single nucleotide polymorphism assay. Results: The frequency of c.1277C allele was higher in AMD patients than in controls (57.2% v 39.3%; p<0.001). The odds ratio (OR; logistic regression analysis) for AMD was 3.9 (95% confidence interval (Cl): 1.9 to 8.2) for CC homozygotes. The CC genotype conferred a higher risk for sporadic (OR 4.6; Cl: 2.0 to 10.5) than for familial AMD (OR 2.9; Cl: 1.0 to 8.4). Genotypes were not related to either age at AMD diagnosis or to AMD phenotype. However, geographic atrophy and choroidal neovascularisation were more frequent in sporadic than in familial AMD (p=0.027). Overall, the percentage of population attributable risk for the CC genotype was 28% (95% Cl:18% to 33%). Conclusion: The association between the p.402Y>H (c.1277T>C) polymorphism and AMD applies to the Italian population and the CC genotype is more frequent in sporadic than in familial AMD cases. [ABSTRACT FROM AUTHOR]

We have investigated the frequency of deletions in the dystrophin gene in 108 unrelated Duchenne and Becker muscular dystrophy (DMD/BMD) patients from southern Italy (DMD, n. 47; BMD, n. 61) and identified 89 deletions. Thede novomutation rate (about 30%), and the preferentially maternal origin of deletional mutations, analysed in families in which the maternal grandparents were available or their haplotypes could be unequivocally reconstructed, are in agreement with data reported for other populations. The correlation between BMD phenotype and type of deletion suggests that, in the distal rod domain region, the deletion size may not be as crucial as the particular combination of missing exons. In fact, we provide immunohistochemical and clinical evidence that in-frame deletion of the hinge III region in the distal rod domain results in a milder phenotype as compared with shorter deletions that do not include the hinge III region. Our data obtained in BMD patients, by confirming inferences arising from minigene transfection experiments inmdxmice, represent an important contribution to gene therapy approaches. [ABSTRACT FROM AUTHOR]