Structural Modelling of KCNQ1 and KCNH2 Double Mutant Proteins, Identified in Two Severe Long QT Syndrome Cases, Reveals New Insights into Cardiac Channelopathies.

Congenital long QT syndrome (LQTS) is a cardiac channelopathy characterized by a prolongation of the QT interval and T-wave abnormalities, caused, in most cases, by mutations in KCNQ1, KCNH2, and SCN5A. Although the predominant pattern of LQTS inheritance is autosomal dominant, compound heterozygous mutations in genes encoding potassium channels have been reported, often with early disease onset and more severe phenotypes. Since the molecular mechanisms underlying severe phenotypes in carriers of compound heterozygous mutations are unknown, it is possible that these compound mutations lead to synergistic or additive alterations to channel structure and function. In this study, all-atom molecular dynamic simulations of KCNQ1 and hERG channels were carried out, including wild-type and channels with compound mutations found in two patients with severe LQTS phenotypes and limited family history of the disease. Because channels can likely incorporate different subunit combinations from different alleles, there are multiple possible configurations of ion channels in LQTS patients. This analysis allowed us to establish the structural impact of different configurations of mutant channels in the activated/open state. Our data suggest that channels with these mutations show moderate changes in folding energy (in most cases of stabilizing character) and changes in channel mobility and volume, differentiating them from each other and from WT. This would indicate possible alterations in K+ ion flow. Hetero-tetrameric mutant channels showed intermediate structural and volume alterations vis-à-vis homo-tetrameric channels. These findings support the hypothesis that hetero-tetrameric channels in patients with compound heterozygous mutations do not necessarily lead to synergistic structural alterations.

Traumatic scalp arteriovenous fistula post capillary implantation successfully treated using PHIL embolic agent.

Background: A traumatic arteriovenous fistula of the scalp due to hair transplantation (AVFHT) is a rare fistulous communication between branches of the arteries and draining veins in the scalp's subcutaneous tissue. Its incidence is unknown and its clinical manifestations may range from a pulsatile mass to seldom epilepsy. Surgery and interventional approaches (percutaneous and endovascular embolization) using coils and embolic agents such as Onyx have been used as treatment options. The authors report a rare case of an AVFHT successfully treated through percutaneous and endovascular embolization using coils and precipitating hydrophobic injectable liquid (PHIL) embolic agent. This is possibly the first reported case using PHIL embolic agent to treat an AVFHT. Case Description: The patient presented with a painful and disabling scalp swelling in the right parieto-occipital region 2 years after a hair transplant in 2011. A computed tomography angiography showed an arteriovenous fistula between branches of the right superficial temporal artery and branches of the right occipital artery to the right superficial temporal vein that was successfully embolized using coils and PHIL. The patient was discharged after a smooth recovery and 1 month later remained healthy. Conclusion: Percutaneous and endovascular embolization using PHIL embolic agent can be an alternative treatment for AVFHT.

3'UTR-CDKN2A and CDK4 Germline Variants Are Associated With Susceptibility to Cutaneous Melanoma.

BACKGROUND/AIM: Genetic variations of the CDKN2A and CDK4 gene have been associated to melanoma development. In the present study we investigated the potential associations of CDKN2A and CDK4 gene variants in a colombian population diagnosed with melanoma. MATERIALS AND METHODS: DNA was extracted from whole blood samples from 85 patients diagnosed with cutaneous melanoma and 166 healthy controls. CDKN2A and CDK4 genes were genotyped using a high-resolution melting assay. RESULTS: A similar distribution of CDKN2A variants 500C>G and 540C>T was found among cases (12% and 31% respectively) and controls (15% and 31% respectively). The CDKN2A variants were present in 36% of acral lentiginous melanoma and 39.47% of lentigo maligna. The haplotype analysis showed an association with susceptibility in the development of melanoma. CONCLUSION: The presence of haplotype 500G/540C in males is associated with an increased risk of melanoma in a colombian population, especially in subjects with a family history of cancer.