A novel mutation in KVLQT1, L122P, found in a family with autosomal dominant long QT syndrome.
BACKGROUND
Linkage and mutation analysis in long QT syndrome kindreds has demonstrated locus heterogeneity, with causative mutations reported in at least 5 different genes, including KVLQT1.


RESULTS
A 12-year-old male proband with recurrent syncope and a prolonged QT interval underwent clinical assessment and exercise testing along with 3 affected and 3 unaffected family members. The coding regions of 5 putative transmembrane segments (S2-S6) and a putative pore region of the KVLQT1 gene for the proband were amplified with the polymerase chain reaction. DNA sequencing of the KVLQT1 gene of the proband revealed a T-->C transversion at the second position of codon 122, which predicted a substitution of proline for leucine (L122P). By using restriction analysis, the L122P was found to be co-segregated with the electrocardiographic abnormalities in the nuclear family. Although the patient's mother was heterozygous for L122P, neither maternal grandparent was a carrier, suggesting that the mutation arose spontaneously. In comparison, there was a complete absence of the mutation in 1336 alleles from 668 normal individuals of 6 different ethnic backgrounds.


CONCLUSIONS
The KVLQT1 L122P mutation is a rare novel mutation that probably arose spontaneously in this family, leading to long QT syndrome.
Krahn
A D
AD
Division of Cardiology and the Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada. akrahn@julian.uwo.ca
Wang
J
J
Spindler
B
B
Skanes
A C
AC
Yee
R
R
Klein
G J
GJ
Hegele
R A
RA
D002648:Child; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics*
D015221:Potassium Channels