Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes / Confirmación diagnóstica molecular mediante secuenciación masiva de nueva generación ("next generation sequencing") en síndromes hereditarios de muerte súbita cardíaca

Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse mutations that cause the altered encoding of the diverse proteins constituting these channels, thus affecting directly the currents of the corresponding ions. In the present article we will briefly review how to arrive to a clinical diagnosis and we will present the results of molecular genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National Institute of Cardiology of Mexico City.

Los síndromes hereditarios de muerte súbita cardíaca comprenden una amplia gama de enfermedades resultantes de la alteración en los canales iónicos cardíacos. Los genes implicados en estos síndromes presentan mutaciones que causan alteraciones de las diversas proteínas que constituyen estos canales y que, por lo tanto, afectan directamente a las diferentes corrientes iónicas. En el presente artículo se revisa brevemente la forma de llegar a un diagnóstico clínico de dichos síndromes y se presentan los resultados de los estudios genéticos moleculares realizados en sujetos mexicanos que asisten a la Clínica de Síndromes Hereditarios de Muerte Súbita del Instituto Nacional de Cardiología Ignacio Chávez.

Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes.

Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse mutations that cause the altered encoding of the diverse proteins constituting these channels, thus affecting directly the currents of the corresponding ions. In the present article we will briefly review how to arrive to a clinical diagnosis and we will present the results of molecular genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National Institute of Cardiology of Mexico City.

Relationship between the angiotensin I-converting enzyme insertion/deletion (I/D) polymorphism and cardiovascular risk factors in healthy young Mexican women.

AIMS: Angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been associated with the genetic susceptibility to several cardiovascular diseases; however, its association with cardiovascular risk factors (CRFs) in different populations needs to be clarified. The purpose of this study was to identify the CRF patterns associated with the ACE I/D polymorphism in women from different Mexican communities. METHODS: ACE I/D polymorphism was determined in two groups of healthy young women: 105 from an urban community and 59 from a semi-urban community using the polymerase chain reaction technique. Distributions of clinical and laboratory profiles among I/D genotypes were analyzed. RESULTS: Women from the semi-urban community had significantly larger waist diameter and higher diastolic blood pressure than women from the urban community (p = 0.003 and p = 0.0055). Differences in the distribution of total cholesterol (p = 0.0008), triglycerides (p = 0.0091), and low-density lipoprotein cholesterol (LDL-C) (p = 0.0272) between genotypes in each community were identified. Women with II genotype had larger values of these CRFs. Estimated risks showed that women from the urban community with the II genotype have three times more risk of having abnormal LDL-C values than women with ID genotype (p = 0.041). Estimated risks between women from semi-urban and urban community showed that urban women have 2.7 and 2.2 times more risk to have abnormal values of LDL-C and high-density lipoprotein cholesterol, respectively (p = 0.010 and p = 0.029), and that women from semi-urban community have three times more risk of having a waist diameter above 80 cm compared to the urban community (p = 0.011). CONCLUSION: The results showed that II homozygous women have higher risk of having high levels lipids and triglycerides than women with ID genotype.

A novel SCN5A deletion mutation in a child with ventricular tachycardia, recurrent aborted sudden death, and Brugada electrocardiographic pattern / Descripción de una nueva mutación (deleción) en el gen SCN5A en un niño con taquicardia ventricular, riesgo de muerte súbita, y cuadro electrocardiográfico de Brugada

A novel SCN5A mutation was found in a child with congenital sick sinus disease, a Brugada-like electrocardiogram and recurrent aborted sudden death. The mutation (L1821fs/10) is a 4 base pair deletion (TCTG) at position 5464-5467 in exon 28 of the gene. The novel mutation is predicted to produce a frameshift leading to a premature stop codon after ten missense amino acids upstream that did not allow the generation of the complete protein, and probably producing an incomplete and therefore non functional protein. The resulting alteration in sodium current could explain the clinical phenotype observed in this patient.

A novel SCN5A deletion mutation in a child with ventricular tachycardia, recurrent aborted sudden death, and Brugada electrocardiographic pattern.

A novel SCN5A mutation was found in a child with congenital sick sinus disease, a Brugada-like electrocardiogram and recurrent aborted sudden death. The mutation (L1821fs/10) is a 4 base pair deletion (TCTG) at position 5464-5467 in exon 28 of the gene. The novel mutation is predicted to produce a frameshift leading to a premature stop codon after ten missense amino acids upstream that did not allow the generation of the complete protein, and probably producing an incomplete and therefore non functional protein. The resulting alteration in sodium current could explain the clinical phenotype observed in this patient.

MHC class II genes in Mexican patients with idiopathic dilated cardiomyopathy.

The purpose of the present study was to evaluate the relationship between class II major histocompatibility complex (MHC) genes (HLA-DR and HLA-DQB) and the genetic susceptibility to idiopathic dilated cardiomyopathy (IDC) in Mexican patients. The HLA-DR and DQB alleles were analyzed in 53 patients with IDC and 99 ethnically matched healthy controls using the polymerase chain reaction-sequence specific oligonucleotides (PCR-SSO) technique. IDC patients showed increased frequencies of HLA-DR4 (pC=0.02, OR=1.87), HLA-DQB1*0301 (pC=0.02, OR=1.92) and HLA-DQB1*0302 (pC=0.02, OR=1.87) when compared to healthy controls. On the other hand, IDC patients also showed decreased frequencies of HLA-DR11 allele (pC=0.03, OR=0.26) and HLA-DQB1*0201 (pC=0.04, OR=0.41). These data suggest that variation in class II HLA alleles could be a genetic factor involved in the susceptibility to IDC of the Mexican Mestizo population.