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PROHLÍŽENÍ ABSTRAKTA
THE HOMOZYGOUS KCNQ1 GENE MUTATION ASSOCIATED WITH RECESSIVE ROMANO-WARD SYNDROME
Tématický okruh: Poruchy rytmu |
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Typ: Ústní sdělení - lékařské , Číslo v programu: 187
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| Novotný T.1, Kadlecová J.2, Janoušek J.3, Gaillyová R.2, Bittnerová A.2, Floriánová A.1, Šišáková M.1, Toman O.4, Chroust K.5, Špinar J.6
1 Interní kardiologická klinika, FN Brno a lékařská fakulta Masarykovy Univerzity, Brno, 2 Oddělení lékařské genetiky, FN Brno, Brno, 3 Kardiocentrum, FN Motol, Praha, 4 Centrum kardiovaskulární péče Brno, Interní kardiologická klinika FN Brno, Brno, 5 Katedra genetiky a molekulární biologie, Masarykova Univerzita, Brno, 6 FN Brno Bohunice
| Background: Mutations in the KCNQ1 gene encoding the α subunit of the IKs channel cause both the recessive Jervell and Lange-Nielsen (homozygous mutation) and more frequent dominant Romano-Ward syndrome (heterozygous mutation), both characterised by a prolonged QT interval, syncope, polymorphic ventricular tachycardia (torsades de pointes) and sudden death. The Jervell and Lange-Nielsen syndrome is also associated with a deafness.
Methods: A family with suspected Romano-Ward syndrome was clinically examined, mutation analysis of KCNQ1 gene was performed.
Results: In a 7-year-old boy with normal hearing suffering with repeated syncopal attacks an extremely prolonged QTc interval (up to 700 ms) was found. The boy´s mother was completely asymptomatic, father had intermitently borderline QTc interval (maximum 470 ms) but no symptoms. In the proband a mutation analysis of KCNQ1 gene revealed a homozygous 1-bp insertion of a C at position 1893 (1893insC) leading to premature stop codon. The parents of the proband were heterozygous for this mutation. They were not aware of any consanguineous marriage in the family.
Conclusions: Our rare finding supports recent data showing that a relatively high number of apparently normal individuals (with normal QT interval) may have a latent reduction of repolarizing currents because they are carriers of ion channel genes polymorphisms. The clinical relevance of this finding in a normal population may be an increased risk of malignant arrhythmias in carriers of such ”mild” mutations under stress condition, e.g. drug challenge or acute ischemia. In near future such polymorphisms could be recognized as inheritable molecular risks of cardiovascular diseases.
The research is supported by IGA MZ CR grants NR/8060-3, NR/8063-3, NR/8374-3 and 1A 8606-5
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