High-efficiency multiplex capillary electrophoresis single strand conformation polymorphism (multi-CE-SSCP) mutation screening of SCN5A: a rapid genetic approach to cardiac arrhythmia.

Mutations in the SCN5A gene coding for the alpha-subunit of the cardiac Na(+) ion channel cause long QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, sick sinus node syndrome, progressive conduction disease, dilated cardiomyopathy and atrial standstill. These diseases exhibit variable expressivity, and identification of gene carriers is clinically important, particularly in sudden infant and adult death syndromes. The SCN5A gene comprises 28 exons distributed over 100 kbp of genomic sequence at chromosome 3p21. Disease-causing mutations are private and scattered over the DNA sequence, making it difficult to screen for specific mutations. We developed a multiplex capillary-electrophoresis single-strand conformation polymorphism (Multi-CE-SSCP) mutation screening protocol on the ABI 3100 platform and applied it to 10 previously slab-gel SSCP identified mutations and SNPs and used it to identify one novel deletion. The method is highly efficient, with a turnover of 23 patients per 24 h and a false positive rate of 0.5% of the analyzed amplicons. Each variant has a particular elution pattern, and all 20 carriers of the H558R polymorphism out of 57 persons were correctly identified. We suggest that the method could become part of routine work-up of patients with suspicious syncope and of members of families with sudden unexplained death.

Prevalence of hyperglycaemia and undiagnosed diabetes mellitus in patients with acute myocardial infarction.

The prevalence of hyperglycaemia and undiagnosed diabetes mellitus was assessed in 214 consecutive patients admitted to the coronary care units with acute myocardial infarction (AMI). On admission, 16 patients (7.5%) had known diabetes, and 19 patients, not previously known to be diabetic, had blood glucose concentrations of greater than or equal to 9 mmol/l. Fifteen patients survived for 2 months at which time a 75 g oral glucose tolerance test showed diabetes in 9 (60%) and impaired glucose tolerance in 4 (27%). Ten of these 13 patients (77%) with abnormal glucose tolerance had elevated glycosylated haemoglobin (HbA1c) on admission, indicating pre-existing glucose intolerance or diabetes. The prevalence of undiagnosed diabetes was 4.5% (9/198). However, we may have overlooked undiagnosed diabetes in a small number of patients on admission, since only a random blood glucose less than 8 mmol/l rules out diabetes, WHO criteria. Elevated blood glucose in patients with AMI is more likely to reflect a stationary pre-existing abnormal glucose tolerance than a temporary stress-induced phenomenon.