Medical education online
Authors: Huppert LA, Hsu G, Elnachef N, Flint L, Frank JA, Gensler LS, Hsiao EC, Khanna RR, Qasim A, Schwartz BS, Widera E, Zapata C, Babik JM
Volume 15 of Issue 1 | Channels (Austin, Tex.)
Authors: Hu RM, Song EJ, Tester DJ, Deschenes I, Ackerman MJ, Makielski JC, Tan BH
: Mutations in SCN5A that decrease Na current underlie arrhythmia syndromes such as the Brugada syndrome (BrS). in humans has two splice variants, one lacking a glutamine at position 1077 (Q1077del) and one containing Q1077. We investigated the effect of splice variant background on loss-of-function and rescue for R1512W, a mutation reported to cause BrS. : We made the mutation in both variants and expressed them in HEK-293 cells for voltage-clamp study. After 24 hours of transfection, the current expression level of R1512W was reduced by ~50% in both Q1077del and Q1077 compared to the wild-type (WT) channel, respectively. The activation and inactivation midpoint were not different between WT and mutant channels in both splice variant backgrounds. However, slower time constants of recovery and enhanced intermediate inactivation were observed for R1512W/Q1077 compared with WT-Q1077, while the recovery and intermediate inactivation parameters of R1512W/Q1077del were similar to WT-Q1077del. Furthermore, both mexiletine and the common polymorphism H558R restored peak sodium current ( ) amplitude of the mutant channel by increasing the cell surface expression of SCN5A. : These findings provide further evidence that the splice variant affects the molecular phenotype with implications for the clinical phenotype, and they provide insight into the expression defect mechanisms and potential treatment in BrS.
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Lancet (London, England)
Authors: Johannson KA, Chaudhuri N, Adegunsoye A, Wolters PJ
Arthritis research & therapy
Authors: Braun J, Blanco R, Marzo-Ortega H, Gensler LS, van den Bosch F, Hall S, Kameda H, Poddubnyy D, van de Sande M, Wiksten AS, Porter BO, Shete A, Richards HB, Haemmerle S, Deodhar A
BMC public health
Authors: Rosenblatt AM, Crews DC, Powe NR, Zonderman AB, Evans MK, Tuot DS
Annals of internal medicine
Authors: Deepak P, Kim W, Paley MA, Yang M, Carvidi AB, Demissie EG, El-Qunni AA, Haile A, Huang K, Kinnett B, Liebeskind MJ, Liu Z, McMorrow LE, Paez D, Pawar N, Perantie DC, Schriefer RE, Sides SE, Thapa M, Gergely M, Abushamma S, Akuse S, Klebert M, Mitchell L, Nix D, Graf J, Taylor KE, Chahin S, Ciorba MA, Katz P, Matloubian M, O'Halloran JA, Presti RM, Wu GF, Whelan SPJ, Buchser WJ, Gensler LS, Nakamura MC, Ellebedy AH, Kim AHJ
Journal of the American Geriatrics Society
Authors: Kotwal AA, Fuller SM, Myers JJ, Hill D, Tha SH, Smith AK, Perissinotto C
Rheumatology (Oxford, England)
Authors: Hwang MC, Lee M, Gensler LS, Brown MA, Tahanan A, Rahbar MH, Hunter T, Shan M, Ishimori ML, Reveille JD, Weisman MH, Learch TJ, PSOAS Study Investigators
Medical decision making : an international journal of the Society for Medical Decision Making
Authors: Khoong EC, Nouri SS, Tuot DS, Nundy S, Fontil V, Sarkar U
Journal of the American Heart Association
Authors: Benjamin EJ, Al-Khatib SM, Desvigne-Nickens P, Alonso A, Djoussé L, Forman DE, Gillis AM, Hendriks JML, Hills MT, Kirchhof P, Link MS, Marcus GM, Mehra R, Murray KT, Parkash R, Piña IL, Redline S, Rienstra M, Sanders P, Somers VK, Van Wagoner DR, Wang PJ, Cooper LS, Go AS
