TY - JOUR
T1 - Mutations in Danish patients with long QT syndrome and the identification of a large founder family with p.F29L in KCNH2
AU - Christiansen, Michael
AU - Hedley, Paula L
AU - Theilade, Juliane
AU - Stoevring, Birgitte
AU - Leren, Trond P
AU - Eschen, Ole
AU - Sørensen, Karina M
AU - Tybjærg-Hansen, Anne
AU - Ousager, Lilian B
AU - Pedersen, Lisbeth N
AU - Frikke-Schmidt, Ruth
AU - Aidt, Frederik H
AU - Hansen, Michael G
AU - Hansen, Jim
AU - Thomsen, Poul Erik Bloch
AU - Toft, Egon
AU - Henriksen, Finn L
AU - Bundgaard, Henning
AU - Jensen, Henrik K
AU - Kanters, Jørgen K
PY - 2014
Y1 - 2014
N2 - BACKGROUND: Long QT syndrome (LQTS) is a cardiac ion channelopathy which presents clinically with palpitations, syncope or sudden death. More than 700 LQTS-causing mutations have been identified in 13 genes, all of which encode proteins involved in the execution of the cardiac action potential. The most frequently affected genes, covering > 90% of cases, are KCNQ1, KCNH2 and SCN5A.METHODS: We describe 64 different mutations in 70 unrelated Danish families using a routine five-gene screen, comprising KCNQ1, KCNH2 and SCN5A as well as KCNE1 and KCNE2.RESULTS: Twenty-two mutations were found in KCNQ1, 28 in KCNH2, 9 in SCN5A, 3 in KCNE1 and 2 in KCNE2. Twenty-six of these have only been described in the Danish population and 18 are novel. One double heterozygote (1.4% of families) was found. A founder mutation, p.F29L in KCNH2, was identified in 5 "unrelated" families. Disease association, in 31.2% of cases, was based on the type of mutation identified (nonsense, insertion/deletion, frameshift or splice-site). Functional data was available for 22.7% of the missense mutations. None of the mutations were found in 364 Danish alleles and only three, all functionally characterised, were recorded in the Exome Variation Server, albeit at a frequency of < 1:1000.CONCLUSION: The genetic etiology of LQTS in Denmark is similar to that found in other populations. A large founder family with p.F29L in KCNH2 was identified. In 48.4% of the mutations disease causation was based on mutation type or functional analysis.
AB - BACKGROUND: Long QT syndrome (LQTS) is a cardiac ion channelopathy which presents clinically with palpitations, syncope or sudden death. More than 700 LQTS-causing mutations have been identified in 13 genes, all of which encode proteins involved in the execution of the cardiac action potential. The most frequently affected genes, covering > 90% of cases, are KCNQ1, KCNH2 and SCN5A.METHODS: We describe 64 different mutations in 70 unrelated Danish families using a routine five-gene screen, comprising KCNQ1, KCNH2 and SCN5A as well as KCNE1 and KCNE2.RESULTS: Twenty-two mutations were found in KCNQ1, 28 in KCNH2, 9 in SCN5A, 3 in KCNE1 and 2 in KCNE2. Twenty-six of these have only been described in the Danish population and 18 are novel. One double heterozygote (1.4% of families) was found. A founder mutation, p.F29L in KCNH2, was identified in 5 "unrelated" families. Disease association, in 31.2% of cases, was based on the type of mutation identified (nonsense, insertion/deletion, frameshift or splice-site). Functional data was available for 22.7% of the missense mutations. None of the mutations were found in 364 Danish alleles and only three, all functionally characterised, were recorded in the Exome Variation Server, albeit at a frequency of < 1:1000.CONCLUSION: The genetic etiology of LQTS in Denmark is similar to that found in other populations. A large founder family with p.F29L in KCNH2 was identified. In 48.4% of the mutations disease causation was based on mutation type or functional analysis.
KW - Case-Control Studies
KW - DNA Mutational Analysis
KW - Denmark
KW - Ether-A-Go-Go Potassium Channels
KW - Female
KW - Founder Effect
KW - Genetic Association Studies
KW - Genetic Predisposition to Disease
KW - Haplotypes
KW - Humans
KW - KCNQ1 Potassium Channel
KW - Long QT Syndrome
KW - Male
KW - Microsatellite Repeats
KW - Mutation, Missense
KW - NAV1.5 Voltage-Gated Sodium Channel
KW - Potassium Channels, Voltage-Gated
U2 - 10.1186/1471-2350-15-31
DO - 10.1186/1471-2350-15-31
M3 - Journal article
C2 - 24606995
SN - 1471-2350
VL - 15
SP - 31
JO - B M C Medical Genetics
JF - B M C Medical Genetics
ER -