Patched homologue 1 mutations in four Japanese families with basal cell nevus syndrome

AIM: To search for patched homologue 1 (PTCH1) mutations in four families with basal cell nevus syndrome (BCNS). METHODS: Mutation analysis of PTCH1 in unrelated Japanese families affected with BCNS was carried out by direct sequencing. RESULTS: Six novel PTCH1 mutations, 833G→A in exon 6, 1415C→A and 1451G→T in exon 10, 2798delC in exon 17, 2918–2925dupAGTTCCCT in exon 18 and 3956C→A in exon 23, were identified. CONCLUSIONS: Among the six PTCH1 mutations, two frameshift mutations (2798delC and 2918–2925dupAGTTCCCT) and one nonsense mutation (833G→A) are predicted to lead to premature termination of PTCH1 protein translation. Three simultaneous mutations, 1415C→A (A472D) and 1451G→T (G484V) in exon 10, and 3956G→A (R1319H) in exon 23, were found on one allele in only affected members in one family and none of them were found among 90 unrelated healthy Japanese. The three mutations on one chromosome may have resulted from errors in the recombinational repair process and this is the first report on the PTCH1 mutations due to such a mechanism

Changes in mitral regurgitation and left ventricular geometry during exercise affect exercise capacity in patients with systolic heart failure.

AIMS: exercise may dramatically change the extent of functional mitral regurgitation (MR) and left ventricular (LV) geometry in patients with chronic heart failure (CHF). We hypothesized that dynamic changes in MR and LV geometry would affect exercise capacity. METHODS AND RESULTS: this study included 30 CHF patients with functional MR who underwent symptom-limited bicycle exercise stress echocardiography and cardiopulmonary exercise testing for quantitative assessment of MR (effective regurgitant orifice; ERO), and pulmonary artery systolic pressure (PASP). LV sphericity index was obtained from real-time three-dimensional echocardiograms. The patients were stratified into exercised-induced MR (EMR; n = 10, an increase in ERO by >/=13 mm(2)) or non-EMR (NEMR; n = 20, an increase in ERO by <13 mm(2)) group. At rest, no differences in LV volume and function, ERO, and PASP were found between the two groups. At peak exercise, PASP and sphericity index were significantly greater (all P < 0.01) in the EMR group. The EMR group revealed lower peak oxygen uptake (peak VO(2); P = 0.018) and greater minute ventilation/carbon dioxide production slope (VE/VCO(2) slope; P = 0.042) than the NEMR group. Peak VO(2) negatively correlated with changes in ERO (r = -0.628) and LV sphericity index (r = -0.437); meanwhile, VE/VCO(2) slope was well correlated with these changes (r = 0.414 and 0.364, respectively). A multivariate analysis identified that the change in ERO was the strongest predictor of peak VO(2) (P = 0.001). CONCLUSION: dynamic changes in MR and LV geometry contributed to the limitation of exercise capacity in patients with CHF

Three-dimensional echocardiographic assessments of exercise-induced changes in left ventricular shape and dyssynchrony in patients with dynamic functional mitral regurgitation.

Aims: Left ventricular (LV) shape and LV dyssynchrony are two cofactors associated with functional mitral regurgitation (MR) in patients with heart failure. Both can be accurately examined by real-time three-dimensional echocardiography (3DE). We examined the relationship between dynamic MR and exercise-induced changes in LV shape and synchronicity using 3DE. Methods and results: Fifty patients with systolic LV dysfunction underwent 2D and 3D quantitative assessment of LV function, shape, and synchronicity at rest and during symptom-limited exercise test. According to the magnitude of change in MR, patients were divided into EMR group (15 patients, 30%), if the degree of MR increased during test, and NEMR group. During exercise, the changes in LV volumes and ejection fraction were similar in both groups, whereas changes in mitral valvular deformation parameters, in LV sphericity index, and in the extent of LV dyssynchrony were more pronounced in the EMR group. At rest, only the 3D sphericity index could distinguish the two groups. By stepwise multiple regression model, dynamic changes in the systolic dyssynchrony index, sphericity index, and coaptation distance were associated with dynamic MR (r2 = 0.45, P = 0.012). Conclusion: Dynamic MR during exercise is related to the 3D changes in LV shape and in LV synchronicity