A New Discovery Of Pathogenic Genes In China For Congenital Long QT Interphase Syndrome Subtype JLN Syndrome

Background:Long QT syndrome(LQTS)is an inherited ion channel disease characterized by abnormal prolongation of the QT interval,syncope,convulsion,and recurrent onset fatal arrhythmia.For patients with untreated LQTS,the 10-year mortality rate can reach up to50%.The root cause of long QT syndrome can be divided into acquired and congenital according to its etiology.Acquired long QT syndrome is mostly caused by drugs,electrolyte disorders,myocardial ischemia and other factors,and the control of induce factors is proved effective in the treatment of acquired long QT syndrome.However,the mechanism of congenital long QT syndrome is relatively complex.In the field of molecular genetics,congenital LQTS can be further divided into Romano-Ward syndrome(RWS)without the phenotype of deafness,and Jervell-Lange-Nielsen syndrome(JLNS)with the phenotype of deafness,based on the current study,the main genetic basis of congenital LQTS in China is KCNQ1,KCNH2 and SCN5 A.Because of the extremely low incidence of JLN syndrome(about 1~6:1000000),the current domestic research is relatively few.This study observed the clinical manifestations and electrocardiogram changes of a family of JLN syndrome from Anhui province,China,and screened a common disease-causing gene of JLNS syndrome,KCNE1,for a series of molecular genetic studies to further understand the pathogenesis and treatment of patients with JLNS syndrome.Purpose:Use gene sequencing technology to analyze gene mutations in a family of JLNS syndrome patients,to study the mutation of KCNE1 gene in JLN syndrome,so as to provide theoretical basis for subsequent gene diagnosis,gene therapy and so on.Method:Investigate the basic condition of a family of JLN syndrome,including whether syncope occurs,the time of first syncope,the frequency of syncope,whether it is accompanied by tip torsional ventricular tachycardia,the length of the electrocardiogram QT interval,QTc,etc.2.Subject to ethical requirements and informed consent,10 members of the family's peripheral blood were collected and genomic DNA was extracted.the KCNE1 gene was sequenced using polymerase chain reaction and DNA two-way sequencing to observe the presence or absence of KCNE1 gene mutations in this JLNS syndrome family.Result:A missense mutation A ? G was found in the KCNE1 gene in the proband as well as in multiple family members,resulting in a change of serine codon(AGT)to glycine codon(GGT).Conclusion:The mutation of KCNE1 gene can lead to JLN syndrome,the 112 th position A ? G missense mutation in KCNE1 gene is the first mutation gene that was found in JLN syndrome in China.