@article {3136471,
	title = {Clinical, genetic, and electrophysiologic characteristics of a new PAS-domain HERG mutation (M124R) causing Long QT syndrome},
	journal = {Ann Noninvasive Electrocardiol},
	volume = {10},
	year = {2005},
	month = {2005 Jul},
	pages = {334-41},
	abstract = {OBJECTIVES: To describe the clinical, genetic, and electrophysiologic characteristics of a new PAS-domain HERG mutation (M124R) that has been identified in a single large Jewish family with Long QT syndrome (LQTS).

BACKGROUND: Many previously reported HERG mutations causing LQTS are located either in the C-terminus, or in the pore region. Relatively fewer clinical data are available on N-terminus (PAS-domain) mutation carriers.

METHODS: Clinical data were available in 76 family members (aged 1-93 years, 69 alive) over 18 years of follow-up, while electrocardiographic data were available in 57, and genetic data in 45 family members. Cellular electrophysiology was assessed in transfected Chinese Hamster Ovary (CHO) cells using the whole-cell patch-clamp technique.

RESULTS: Thirty-six family members were phenotypically categorized as nonaffected, 3 as equivocal, and 20 as affected. Mean QTc was 410+/-23, 440+/-10, and 498+/-41 ms, respectively, in these three subgroups. Eight out of 20 affected family members were symptomatic: five had only syncope, two had aborted cardiac arrest, and one sudden death. Genetic analyses identified the M124R point mutation in all affected members tested (n=16), while all those tested with nonaffected (n=26) and equivocal (n=3) phenotype did not carry the mutation. The M124R mutation reduced the HERG tail-current density by 65\%, significantly accelerated the deactivation kinetics, and caused a negative shift in the voltage dependence of activation.

CONCLUSIONS: A new PAS-domain HERG mutation (M124R) was identified as causing LQTS in a large Jewish family, with high penetrance and frequent disease-related symptoms. This mutation markedly decreased the tail-current density and accelerated the deactivation kinetics of the HERG channel in transfected CHO cells.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Electrocardiography, ERG1 Potassium Channel, Ether-A-Go-Go Potassium Channels, Female, GENOTYPE, Humans, Infant, ISRAEL, Long QT Syndrome, Male, Middle Aged, Mutation, Pedigree, Phenotype, Potassium Channels, Voltage-Gated, Sequence Analysis},
	issn = {1082-720X},
	doi = {10.1111/j.1542-474X.2005.00643.x},
	author = {Shushi, Liat and Kerem, Batsheva and Goldmit, Maya and Peretz, Asher and Attali, Bernard and Medina, Aron and Towbin, Jeffrey A and Kurokawa, Junko and Kass, Robert S and Benhorin, Jesaia}
}
