Mutation detection in long QT syndrome: a comprehensive set of primers and PCR conditions

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Abstract
Editor—Long QT syndrome (LQTS) is an inherited disorder which produces arrhythmia and sudden death. The only presymptomatic indication of the disorder is an extended QT interval, in excess of 460 ms.1 However, those with LQTS do not always show this prolongation of QT. There are dominantly and recessively inherited forms of the disease, Romano-Ward syndrome and Jervell Lange-Nielsen syndrome, respectively, the latter also exhibiting severe sensorineural deafness.2-4 About half the familial cases of LQT are known to be caused by mutations in five ion channel or channel associated genes, with over 90% being accounted for by KCNQ1 and HERG , both of which code for potassium channels.5 The sodium channel gene SCN5A is responsible for about 8% of cases with a known gene mutation, while KCNE1 and KCNE2 , which code for proteins that associate with KCNQ1 and HERG respectively, are mutated in 1-2%.5 Mutations in KCNQ1 can produce both dominant and recessive forms of the disease, depending on the nature of the mutation.6-12 HERG and SCN5A mutations are dominant, while those in KCNE1 and KCNE2 are recessive.13-16There are, however, exceptions to these rules.17 18 Mutations have been identified throughout the genes,19 20although analysis of both HERG and SCN5A has tended to be concentrated on the pore regions owing to the substantial number of exons in both genes. The initial publications on KCNQ1 (formerly KVLQT1 ) also analysed the pore and surrounding regions, although several groups have now produced primers that cover the entire gene.19 21 The mutation analysis has been by PCR followed by SSCP, and although laborious, this is still the most commonly used method. Investigation of all the genes has not been possible, mainly because the exact sequence of the PCR fragments amplified by the …

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