[The mutation scanning of KCNQ1 gene for 31 long QT syndrome families].
OBJECTIVE
To search for the mutations of potassium voltage-gated channel, KQT-like subfamily member 1(KCNQ1) gene in 31 Chinese long QT syndrome(LQTS) families.


METHODS
Due to the genetic heterogeneity, the genotype of patients was first predicted based on the spectrum of ST-T-wave patterns on ECG. Ten of 31 probands were considered as LQT1. Then the mutation of KCNQ1 gene was screened by the polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) technique combined with DNA sequencing in all members of these 10 families. To avoid omitting some LQT1 patients without typical characteristics and also to do methodological comparison, the mutations of KCNQ1 gene on 16 exons were screened by PCR and direct DNA sequencing in the rest 21 non-LQT1 probands only. Co-segregation analysis was carried out after the finding of an abnormal sequence. In case that the abnormality existed in patients only, the test of such exon was performed in 50 irrelevant normal individuals.


RESULTS
Two missense mutations and three single nucleotide polymorphisms (SNPs) were found in the LQT1 predicted families. The two mutations were S277L (1 family) and G306V (1 family) in exon 5 and were not reported previously. Three polymorphisms were 435C-->T (7 families), 1632C-->A (1 family), and IVS1+9 C-->G (3 families). Only a splice mutation IVS1+5G-->A (2 families) and a polymorphism IVS10+18C-->T (1 family) were found in the non-LQT1 predicted probands. All three mutations were localized within the functional domain of KCNQ1 and were co-segregated with the disease, and were not found in 50 normal individuals.


CONCLUSIONS
Two novel missense mutations, 1 splice mutation and four SNPs on KCNQ1 gene were found in the 31 LQTS families. Combined with ECG-based genotype prediction, PCR-SSCP could find most mutations on KCNQ1 and be a simple and economic method for screening LQTS.
Li
Ping
P
Department of Cardiology, People's Hospital of Peking University, Beijing, 100044 PR China.
Li
Cui-lan
CL
Hu
Da-yi
DY
Liu
Wen-ling
WL
Qin
Xu-guang
XG
Li
Yun-tian
YT
Li
Zhi-ming
ZM
Li
Lei
L
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated
D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated