TY - JOUR
T1 - Multiple different missense mutations in the pore region of HERG in patients with long QT syndrome
AU - Satler, Carol Ann
AU - Vesely, Mark R.
AU - Duggal, Priya
AU - Ginsburg, Geoffrey S.
AU - Beggs, Alan H.
N1 - Funding Information:
Acknowledgements We are grateful to the LQTS families whose participation made this investigation possible. We also acknowledge the invaluable assistance of Christine Dindy, Alexa Laurent, and Alessandro Nardi. We thank the many physicians who have provided LQTS patient samples, especially Drs. J. Allender, F. Cecchin, L. Cohn, G. Van Hare, J. Kron, and J. McCormack, whose families are described here. We are also thankful for the helpful support and advice of Drs. Howard Jacob, Edward Walsh, Louis Kunkel, Carsten Bönnemann, Gary Yellen, and David Clapham. Dr. Satler is the recipient of a Clinical Investigator Development Award from the National Heart, Lung and Blood Institute (5K08-HL02786). Dr. Beggs was supported by K02 AR02026 from the NIAMS. This study was also supported by research grants from the Edward Mallinckrodt Jr. Foundation, the Gustavus and Louise Pfeiffer Research Foundation, the Charles H. Hood Foundation, R01 AR44345 from the NIAMS, and the Boston Children’s Hospital Department of Cardiology. Additional support was provided by the Hewlett-Packard Company and Marquette Electronics. These experiments comply with the current laws of the country in which they were performed.
PY - 1998
Y1 - 1998
N2 - Long QT syndrome (LQTS), is an inherited cardiac disorder in which ventricular tachyarrhythmias predispose affected individuals to syncope, seizures, and sudden death. Characteristic electrocardiographic findings include a prolonged QT interval, T wave alternans, and notched T waves. We have screened LQTS patients from 89 families for mutations in the pore region of HERG, the K+ channel gene previously associated with chromosome 7-linked LQT2. In six unrelated LQTS kindreds, single-strand conformation polymorphism analyses identified aberrant conformers in all affected family members. These conformers were not seen in over 100 unaffected, unrelated control individuals, suggesting that they represent pathogenic LQTS mutations. DNA sequence analyses of the aberrant conformers demonstrated that they reflect five different missense mutations: V612L, A614V, N629D, N629S, and N633S. The missense mutation A614V was found in two unrelated families. Further functional studies will be required to determine what effect each of these changes may have on HERG channel function.
AB - Long QT syndrome (LQTS), is an inherited cardiac disorder in which ventricular tachyarrhythmias predispose affected individuals to syncope, seizures, and sudden death. Characteristic electrocardiographic findings include a prolonged QT interval, T wave alternans, and notched T waves. We have screened LQTS patients from 89 families for mutations in the pore region of HERG, the K+ channel gene previously associated with chromosome 7-linked LQT2. In six unrelated LQTS kindreds, single-strand conformation polymorphism analyses identified aberrant conformers in all affected family members. These conformers were not seen in over 100 unaffected, unrelated control individuals, suggesting that they represent pathogenic LQTS mutations. DNA sequence analyses of the aberrant conformers demonstrated that they reflect five different missense mutations: V612L, A614V, N629D, N629S, and N633S. The missense mutation A614V was found in two unrelated families. Further functional studies will be required to determine what effect each of these changes may have on HERG channel function.
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U2 - 10.1007/s004390050690
DO - 10.1007/s004390050690
M3 - Article
C2 - 9544837
AN - SCOPUS:0031948555
SN - 0340-6717
VL - 102
SP - 265
EP - 272
JO - Human genetics
JF - Human genetics
IS - 3
ER -