856 Rev Esp Cardiol. 2010;63(7):856-9 The Spectrum of SCN5A Gene Mutations in Spanish Brugada Syndrome Patients Mónica García-Castro, a Cristina García, a Julián R. Reguero, b Ana Miar, a José M. Rubín, b Victoria Álvarez, a César Morís, b and Eliecer Coto a,c a Genética Molecular, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain b Servicio de Cardiología, Fundación Asturcor, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain c Instituto de Investigación Nefrológica-Fundación Renal Íñigo Álvarez de Toledo, Madrid, Spain BRIEF REPORT Study funded by grants from the Spanish Health Research Fund and European Regional Development Fund (project FIS-06/0214; principal investigator, Eliecer Coto García) and from the Red de Investigación Renal-REDINREN (RD06/0016) of the Carlos III Health Institute. Correspondence: Dr. E. Coto. Laboratorio de Genética Molecular. Hospital Universitario Central de Asturias (Maternidad). 33006 Oviedo. Asturias. Spain. E-mail: eliecer.coto@sespa.princast.es Manuscript received May 8, 2009. Accepted for publication July 31, 2009. Brugada syndrome is characterized by right bundle branch block and ST-segment elevation in the right precordial ECG leads. Familial transmission is frequent and approximately 25% of cases exhibit mutations in the SCN5A gene. We analyzed the sequence of this gene in 25 Spanish patients with Brugada syndrome. In 4 (16%), we found mutations that had not previously been described: three were amino acid changes (i.e. Ala2>Thr, Ala735>Thr and Val1340>Ile) and one was an intron mutation that affected messenger RNA processing (i.e. IVS18-1G>A). These four patients had relatives who were also mutation carriers, several of whom had normal ECGs, even on flecainide challenge. Our study suggests that genetic analysis could be helpful in the presymptomatic diagnosis of Brugada syndrome, but may be less useful for stratifying the risk of adverse events. Key words: Brugada syndrome. SCN5A gene. Mutations. Genetic risk. Espectro mutacional del gen SCN5A en pacientes españoles con síndrome de Brugada El síndrome de Brugada se caracteriza por un bloqueo de la rama derecha y elevación del segmento ST en las derivaciones precordiales derechas del electrocardiogra- ma. Con frecuencia se observa una transmisión familiar, y en aproximadamente el 25% de los casos se han ha- llado mutaciones en el gen SCN5A. Hemos analizado la secuencia de este gen en 25 pacientes españoles con síndrome de Brugada. En 4 de ellos (16%) hallamos mu- taciones que no habían sido descritas previamente: 3 eran cambios de aminoácidos (Ala2>Tre, Ala735>Tre y Val1340>Ile) y 1 era intrónica y afectaría al procesamien- to del ARNm (intrón 18 IVS18-1G>A). En los 4 había fami- liares portadores, y varios de ellos tenían electrocardio- gramas normales, incluso tras inducción con flecainida. Nuestro estudio indica que el análisis genético sería útil para el diagnóstico presintomático, pero de utilidad limi- tada para estratificar el riesgo de eventos adversos. Palabras clave: Síndrome de Brugada. Gen SCN5A. Mutaciones. Riesgo genético. INTRODUCTION Brugada syndrome is a cardiac arrhythmia characterized by right bundle branch block and ST elevation in the right precordial leads of the electrocardiogram (ECG) in the absence of structural heart disease. 1 In many cases it is difficult to distinguish between Brugada syndrome and other arrhythmias, although it can be unmasked with sodium channel blockers. 2 The syndrome is associated with an increased risk of sudden death, sometimes during infancy. It can be diagnosed from a few days after birth until adulthood and the mean age of sudden death is around 40 years. The prevalence is around 5 cases per 10 000 inhabitants, although the ECG may appear normal in many individuals with the syndrome, making the true frequency difficult to determine. Brugada syndrome may be responsible for around 20% of sudden deaths in men younger than 40 years with structurally normal hearts. Many patients have a family history of the disease, which follows an autosomal dominant pattern of inheritance. In 25% of patients, mutations are present in the SCN5A gene, which encodes an alpha subunit of the cardiac sodium channel. 3-5 More than 100 different SCN5A mutations have been described Document downloaded from http://www.revespcardiol.org, day 27/07/2011. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.