Sudden cardiac death in persons aged 50 years or younger: diagnostic yield of a regional molecular autopsy program using massive sequencing.

INTRODUCTION AND OBJECTIVES: Sudden cardiac death (SCD) in young people often has a genetic cause. Consequently, the results of "molecular autopsy" may have important implications for their relatives. Our objective was to evaluate the diagnostic yield of a molecular autopsy program using next-generation sequencing. METHODS: We performed a prospective study of a cohort of consecutive patients who died from nonviolent SCD, aged ≤ 50 years, and who underwent molecular autopsy using large panels of next-generation sequencing, with subsequent clinical and genetic family screening. We analyzed demographic, clinical, toxicological, and genetic data. RESULTS: We studied 123 consecutive cases of SCD in persons aged ≤ 50 years. The incidence of SCD was 5.8 cases/100 000 individuals/y, mean age was 36.15±12.7 years, and 95 were men (77%). The cause was cardiac in 53%, unexplained SCD in 24%, toxic in 10.6%, and infant SCD in 4%. Among cardiac causes, ischemic heart disease accounted for 38% of deaths, arrhythmogenic cardiomyopathy for 7%, hypertrophic cardiomyopathy for 5%, and idiopathic left ventricular hypertrophy for 11%. Genetic analysis was performed in 62 cases (50.4%). Genetic variants were found in 42 cases (67.7%), with a mean of 3.4±4 genetic variants/patient, and the variant found was considered to be pathogenic or probably pathogenic in 30.6%. In unexplained SCD, 70% showed some genetic variant. Family screening diagnosed 21 carriers or affected individuals, 5 of whom were at risk, indicating an implantable cardiac defibrillator. CONCLUSIONS: Protocol-based and exhaustive study of SCD from cardiac causes in persons aged ≤ 50 years is feasible and necessary. In a high percentage of cases, the cause is genetic, indicating the existence of relatives at risk who could benefit from early diagnosis and treatment to avoid complications.

La identificación genética como herramienta en la investigación de adopciones irregulares y sustracción de recién nacidos en España: experiencia del Instituto Nacional de Toxicología y Ciencias Forenses (Departamento de Barcelona) / Genetic identification as a tool in research of irregular adoptions and abduction of newborns in Spain: National Institute of Toxicology and Forensic Science (Department of Barcelona) experience

Introducción. Los casos de adopciones irregulares y sustracción de recién nacidos en España han tenido una gran repercusión social, lo que ha conllevado la elaboración de reformas normativas y el desarrollo de guías y recomendaciones científicas que ayuden a su investigación. El objetivo del presente estudio fue la identificación genética de las muestras remitidas mediante estudios de parentesco. Material y métodos. Entre 2011-2014 se recibieron en el Departamento de Barcelona del Instituto Nacional de Toxicología y Ciencias Forenses 58 casos sobre los que se requirió judicialmente un estudio de identificación genética. Se analizaron restos óseos exhumados o muestras clínicas. Tras el estudio previo (antropológico y anatomopatológico) se procedió a la extracción del material genético y su posterior análisis. Resultados. La calidad y cantidad del ADN recuperado permitió el análisis genético en el 67,2% de los casos, frente al 32,8% donde no fue posible. Los datos muestran que mayoritariamente (87,2%) se estableció una relación de compatibilidad paterno-filial, siendo minoritarias las exclusiones (12,8%). El índice de verosimilitud osciló entre 1,75 × 104-5,95 × 1017 y los STR estudiados de 8-21. Conclusiones. Los datos y experiencia adquirida muestran la importancia de la recopilación de la información, de los antecedentes del caso y del estudio antropológico previamente al análisis genético. Esta información permite orientar los estudios genéticos y, ocasionalmente, ayuda a interpretar los resultados. Asimismo, las características de este tipo de muestras obligan a establecer un protocolo de calidad que garantice la autenticidad de los resultados finales (AU)

Introduction. Cases of irregular adoptions and abduction of newborns in Spain have had got a great social impact which has led to regulatory reforms and the implementation of scientific guidelines and recommendations to help their investigation. The objective of the study was the genetic identification of the samples submitted by kinship studies. Materials and methods. In the period between the year 2011 and 2014, the Barcelona Department of the National Institute of Toxicology and Forensic Sciences,received a total of 58 cases on which it was judicially required to carry out a study of genetic identification. Exhumed bones or clinical samples were analyzed. After previous study (anthropological, anatomo-pathological), the extraction of genetic material and its subsequent analysis were carried out. Results. The quality and the quantity of recovered DNA allowed carrying out genetic analysis in 67.2% of cases, compared to 32.8%, where it was not possible. The data show that for the majority ofthe cases studied (87.2%) was established a positive relationship, being minority the cases of exclusion (12.8%). The likelihood ratio (LR) obtained, ranged from 1.75 × 104-5.95 × 1017, and the STR markers studied from 8 to 21. Conclusions. Experience and data show the importance of gathering information, the history related to the caseand the importance of the anthropological study prior to genetic analysis. This information allows orienting the genetic studies and, in some cases, it helps to interpret the results. Also, the characteristics of this type of samples require establishing a quality protocol that ensures the authenticity of the final results (AU)