Sanger sequencing as a first-line approach for molecular diagnosis of Andersen-Tawil syndrome [version 1; peer review: 3 approved]

• Published in: F1000 research Vol. 6; p. 1016
• Main Authors: Totomoch-Serra, Armando, Marquez, Manlio F, Cervantes-Barragán, David E
• Format: Journal Article
• Language: English
• Published: England Faculty of 1000 Ltd 2017; F1000Research; F1000 Research Ltd
• Subjects: Andersen's syndrome; Base pairs; Cardiovascular diseases; Channelopathy; Deoxyribonucleic acid; Diagnosis; DNA; DNA sequencing; EKG; Exons; Genetics; Genomics; KCNJ2 gene; Mutation; Nucleotide sequence; Opinion; Potassium; Potassium channels (inwardly-rectifying); Proteins; Sanger, Frederick; Ventricle; clinical diagnosis; mutation; Andersen-Tawil; genetic testing; Sanger sequencing; KCNJ2; Next Generation Sequencing
• ISSN: 2046-1402; 2046-1402
• DOI: 10.12688/f1000research.11610.1

In 1977, Frederick Sanger developed a new method for DNA sequencing based on the chain termination method, now known as the Sanger sequencing method (SSM).  Recently, massive parallel sequencing, better known as next-generation sequencing (NGS),  is replacing the SSM for detecting mutations in cardiovascular diseases with a genetic background. The present opinion article wants to remark that "targeted" SSM is still effective as a first-line approach for the molecular diagnosis of some specific conditions, as is the case for Andersen-Tawil syndrome (ATS). ATS is described as a rare multisystemic autosomal dominant channelopathy syndrome caused mainly by a heterozygous mutation in the KCNJ2 gene . KCJN2 has particular characteristics that make it attractive for "directed" SSM. KCNJ2 has a sequence of 17,510 base pairs (bp), and a short coding region with two exons (exon 1=166 bp and exon 2=5220 bp), half of the mutations are located in the C-terminal cytosolic domain, a mutational hotspot has been described in residue Arg218, and this gene explains the phenotype in 60% of ATS cases that fulfill all the clinical criteria of the disease. In order to increase the diagnosis of ATS we urge cardiologists to search for facial and muscular abnormalities in subjects with frequent ventricular arrhythmias (especially bigeminy) and prominent U waves on the electrocardiogram.