Mutation in KCNQ1 that has both recessive and dominant characteristics

• Published in: Journal of medical genetics 2002-09, Vol.39 (9), p.681-685
• Main Authors: Murray, A, Potet, F, Bellocq, C, Baró, I, Reardon, W, Hughes, H E, Jeffery, S
• Format: Article
• Language: English
• Subjects: Abnormalities; Animals; Biological and medical sciences; Brain damage; Cardiac arrest; Cardiac dysrhythmias; Cardiology. Vascular system; Causes of; Child, Preschool; Consanguinity; COS Cells; Cytomegalovirus; Death; DNA - chemistry; DNA - genetics; DNA Mutational Analysis; Electrophysiology; Fainting; Familial diseases; Family Health; Fatal Outcome; Female; Gene mutations; Genes; Genes, Dominant - genetics; Genes, Recessive - genetics; Genetic aspects; Hearing loss; Heart; Humans; inheritance; Ion channels; Jervell-Lange-Nielsen syndrome; JLNS; KCNQ Potassium Channels; KCNQ1; KCNQ1 Potassium Channel; Letter to JMG; long QT syndrome; Long QT Syndrome - genetics; LQTS; Male; Medical sciences; Membrane Potentials - genetics; Membrane Potentials - physiology; Molecular biology; Mutation; Mutation (Biology); Mutation, Missense; Patch-Clamp Techniques; Pedigree; Phenotype; Physiological aspects; Plasmids; Plasmids - genetics; Polymorphism, Single-Stranded Conformational; Potassium Channels - genetics; Potassium Channels, Voltage-Gated; Proteomics; Rodents; Romano-Ward syndrome; RWS; wild type
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.39.9.681

Mutations in KCNQ1 produce JLNS as well as RWS, 10- 12 although in the latter case there appears to be a strongly dominant negative effect exerted by the mutant protein, while this is very weak or absent in mutant proteins which produce JLNS. 13 Three reports have shown that RWS can be inherited in a recessive manner. 14- 16 One of these families was a compound heterozygote, where there were extended QT intervals seen for both heterozygotes, 14 but the other two families had no heterozygotes with QTc above 450 ms. 15, 16 These were therefore recessive both for the effect on QT interval and for clinical manifestations. Stimulation data recording and analysis were performed through an analogue to digital converter (Tecmar TM100 Labmaster, Scientific Solutions, Solon, OH) and Acquis1 software (Bio-Logic, Claix, France).\n The other two families were also recessive in terms of the QT interval exhibited for heterozygotes, in that none of the gene carriers had a QTc greater than 450 ms. 15, 16 In the family presented here, there are two in excess of 460 ms, the top cut off for any studies on LQTS. [...]for ECG analysis this is a dominantly inherited trait with reduced penetrance, but clinically it shows recessive inheritance.