2.50
Hdl Handle:
http://hdl.handle.net/10755/159010
Type:
Presentation
Title:
A Dominant Negative HERG Mutation Causes Neonatal Long QT Syndrome
Abstract:
A Dominant Negative HERG Mutation Causes Neonatal Long QT Syndrome
Conference Sponsor:Midwest Nursing Research Society
Conference Year:2006
Author:Beery, Theresa, PhD, ACNP, RN
P.I. Institution Name:University of Cincinnati
Title:Associate Professor
Contact Address:College of Nursing, 3110 Vine St., Cincinnati, OH, 45221-0038, USA
Contact Telephone:513-558-5006
Co-Authors:Kerry Shooner, MS, CGC, Cardiovascular Specialist and D. Woodrow Benson, MD, PhD, Professor
The potassium ion channel HERG is responsible for 45% of identified mutations causing Long QT Syndrome. Loss of function is the most common mechanism for the nearly 90 reported HERG mutations. Fewer than 20 of these function in a dominant negative fashion, suppressing the function of the wildtype allele in the heterozygote. The proband in this study was an apparently healthy newborn female with onset of choking, gasping, and cyanosis at home when 4 days old. A second episode with arching and cyanosis occurred in the emergency department. A 12-Lead ECG documented a substantially lengthened QTc of 637 ms. An echocardiogram was read as normal. No QT prolongation was seen on the electrocardiograms of her parents. Due to the child's severe phenotype compound heterozygosity was suspected. DNA isolated from whole blood was screened for mutations in the ion channel genes KCNQ1, HERG, SCN5A, KCNE1 and KCNE2. The previously documented mutation A561V (1682 C->T) located in the S5 transmembrane domain of HERG was found via sequencing. Neither parent carried this mutation. No additional sequence variations were found. The HERG A561V mutation produces a channel trafficking defect with protein retention in the endoplasmic reticulum. It functions in a dominant negative manner suppressing channel trafficking of the wildtype. Tetramers with at least two mutant subunits do not localize to the membrane. The dominant negative effect of this mutation is the likely cause of the severe phenotype documented in this child.
Repository Posting Date:
26-Oct-2011
Date of Publication:
17-Oct-2011
Sponsors:
Midwest Nursing Research Society

Full metadata record

DC FieldValue Language
dc.typePresentationen_GB
dc.titleA Dominant Negative HERG Mutation Causes Neonatal Long QT Syndromeen_GB
dc.identifier.urihttp://hdl.handle.net/10755/159010-
dc.description.abstract<table><tr><td colspan="2" class="item-title">A Dominant Negative HERG Mutation Causes Neonatal Long QT Syndrome</td></tr><tr class="item-sponsor"><td class="label">Conference Sponsor:</td><td class="value">Midwest Nursing Research Society</td></tr><tr class="item-year"><td class="label">Conference Year:</td><td class="value">2006</td></tr><tr class="item-author"><td class="label">Author:</td><td class="value">Beery, Theresa, PhD, ACNP, RN</td></tr><tr class="item-institute"><td class="label">P.I. Institution Name:</td><td class="value">University of Cincinnati</td></tr><tr class="item-author-title"><td class="label">Title:</td><td class="value">Associate Professor</td></tr><tr class="item-address"><td class="label">Contact Address:</td><td class="value">College of Nursing, 3110 Vine St., Cincinnati, OH, 45221-0038, USA</td></tr><tr class="item-phone"><td class="label">Contact Telephone:</td><td class="value">513-558-5006</td></tr><tr class="item-email"><td class="label">Email:</td><td class="value">theresa.beery@uc.edu</td></tr><tr class="item-co-authors"><td class="label">Co-Authors:</td><td class="value">Kerry Shooner, MS, CGC, Cardiovascular Specialist and D. Woodrow Benson, MD, PhD, Professor</td></tr><tr><td colspan="2" class="item-abstract">The potassium ion channel HERG is responsible for 45% of identified mutations causing Long QT Syndrome. Loss of function is the most common mechanism for the nearly 90 reported HERG mutations. Fewer than 20 of these function in a dominant negative fashion, suppressing the function of the wildtype allele in the heterozygote. The proband in this study was an apparently healthy newborn female with onset of choking, gasping, and cyanosis at home when 4 days old. A second episode with arching and cyanosis occurred in the emergency department. A 12-Lead ECG documented a substantially lengthened QTc of 637 ms. An echocardiogram was read as normal. No QT prolongation was seen on the electrocardiograms of her parents. Due to the child's severe phenotype compound heterozygosity was suspected. DNA isolated from whole blood was screened for mutations in the ion channel genes KCNQ1, HERG, SCN5A, KCNE1 and KCNE2. The previously documented mutation A561V (1682 C-&gt;T) located in the S5 transmembrane domain of HERG was found via sequencing. Neither parent carried this mutation. No additional sequence variations were found. The HERG A561V mutation produces a channel trafficking defect with protein retention in the endoplasmic reticulum. It functions in a dominant negative manner suppressing channel trafficking of the wildtype. Tetramers with at least two mutant subunits do not localize to the membrane. The dominant negative effect of this mutation is the likely cause of the severe phenotype documented in this child.</td></tr></table>en_GB
dc.date.available2011-10-26T21:36:54Z-
dc.date.issued2011-10-17en_GB
dc.date.accessioned2011-10-26T21:36:54Z-
dc.description.sponsorshipMidwest Nursing Research Societyen_GB
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