Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A)

Sick sinus syndrome (SSS) describes an arrhythmia phenotype attributed to sinus node dysfunction and diagnosed by electrocardiographic demonstration of sinus bradycardia or sinus arrest. Although frequently associated with underlying heart disease and seen most often in the elderly, SSS may occur in the fetus, infant, and child without apparent cause. In this setting, SSS is presumed to be congenital. Based on prior associations with disorders of cardiac rhythm and conduction, we screened the α subunit of the cardiac sodium channel (SCN5A) as a candidate gene in ten pediatric patients from seven families who were diagnosed with congenital SSS during the first decade of life. Probands from three kindreds exhibited compound heterozygosity for six distinct SCN5A alleles, including two mutations previously associated with dominant disorders of cardiac excitability. Biophysical characterization of the mutants using heterologously expressed recombinant human heart sodium channels demonstrate loss of function or significant impairments in channel gating (inactivation) that predict reduced myocardial excitability. Our findings reveal a molecular basis for some forms of congenital SSS and define a recessive disorder of a human heart voltage-gated sodium channel

Carbazole substituted BODIPYs: synthesis, computational, electrochemical and DSSC studies

Carbazole and p-anisyl substituted BODIPY dyes with a cyanoacetic acid anchoring group have been prepared and their spectral, electrochemical properties and photosensitizing potential in DSSC have been evaluated. X-ray structure of N-phenylcarbazole substituted BODIPY revealed lower torsion angle between BODIPY plane and carbazole plane, suggesting increased communication between the two units. DFT studies indicated effective electronic interactions between the BODIPY unit and carbazole substituents. The N-butylcarbazole and N-phenylcarbazole substituted BODIPYs showed anodic shifts in their reduction potentials, indicating facile reduction process. The predicted HOMO-LUMO gaps are in agreement with the electrochemical result and the lower band gap was observed for the carbazole substituted BODIPYs.by by Praseetha E. Kesavan, Raghu Nath Behera, Shigeki Mori and Iti Gupt