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

Ripoll‐Vera, Tomás; Luengo, Consuelo Pérez; Alcázar, Juan Carlos Borondo; Ruíz, Ana Belén Mirete; Valle, Nieves Sánchez Del; Martín, Bernardino Barceló; García, Juan Luis Poncela; Buitrago, Gloria Gutiérrez; Martínez, C. Dasi; Villena, Juan Carlos Canós; Corvillo, Susana Moyano; Pallarés, Raquel Esgueva; Sancho, Juan Ramón Sancho; Pinedo, Gemma Guitart; Marín, Elena Hernández; García, Estela García; López, Albert Vingut; Rubio, Judit; Callizo, Nancy Govea; Pérez, Yolanda Gómez; Mesquida, C Melia; Heine, Damián; Andreo, Jordi Rosell; Crespí, Lorenzo Socías

doi:10.1016/j.rec.2020.03.030

Cited by 11 publications

(8 citation statements)

References 27 publications

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“…The genetic test, as a fundamental investigation for the post-mortem assessment of HCM, was reported in several studies [26,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53]. The related data obtained from the articles are summarized in Table 2.…”

Section: Molecular Autopsymentioning

confidence: 99%

“…Genes codifying sarcomeric protein were the most frequently involved, with a prevalence for the mutation of MYBPC3 (Myosin-binding protein C) [26,[39][40][41][43][44][45][47][48][49][50]52], in which 12 pathogenic or likely pathogenic variants were reported (c.2221delG; c.3491-2A>T; p.Gln969Ter; p.Phe295SerfsTer5; p.Gly278GlufsTer22; c.649A>G; c.150C>A; c.2003G>A; c.1504C>T; c.442G>A; p.Arg726Cys; c.2441_2443del). Then, mutations were observed at MYH7 (Myosin heavy chain 7) [38][39][40][41]43,44,[46][47][48][49][50] with nine variants classified as pathogenic or likely pathogenic (c.1325G>A; R249Q; c.5120T>C; (c.3134G>T; Thr446Pro; Phe468Leu; p.Arg652Lys; c.2105T>A; c.G2348T). Other pathogenic and likely pathogenic variants were found at MYH6 (Myosin heavy chain 6; c.4193G>A) [43], ACTN2 (Actinin α2; c.355G>A) [51], TNNT2 (Troponin T type 2; c.517_519de) [50], TPM1 (Tropomyosin 1α¸c.656A>T) [53], and TTN (Titin; c.48163C>T) [43].…”

Section: Molecular Autopsymentioning

confidence: 99%

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Morphological and Genetic Aspects for Post-Mortem Diagnosis of Hypertrophic Cardiomyopathy: A Systematic Review

Cianci,

Forzese,

Sapienza

et al. 2024

IJMS

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Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be clinically silent, and sudden unexpected death due to malignant arrhythmias may be the first manifestation. Thus, the HCM diagnosis could be performed at a clinical and judicial autopsy and offer useful findings on morphological features; moreover, it could integrate the knowledge on the genetic aspect of the disease. This review aims to systematically analyze the literature on the main post-mortem investigations and the related findings of HCM to reach a well-characterized and stringent diagnosis; the review was performed using PubMed and Scopus databases. The articles on the post-mortem evaluation of HCM by gross and microscopic evaluation, imaging, and genetic test were selected; a total of 36 studies were included. HCM was described with a wide range of gross findings, and there were cases without morphological alterations. Myocyte hypertrophy, disarray, fibrosis, and small vessel disease were the main histological findings. The post-mortem genetic tests allowed the diagnosis to be reached in cases without morpho-structural abnormalities; clinical and forensic pathologists have a pivotal role in HCM diagnosis; they contribute to a better definition of the disease and also provide data on the genotype–phenotype correlation, which is useful for clinical research.

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Section: Molecular Autopsymentioning

confidence: 99%

Section: Molecular Autopsymentioning

confidence: 99%

Morphological and Genetic Aspects for Post-Mortem Diagnosis of Hypertrophic Cardiomyopathy: A Systematic Review

Cianci,

Forzese,

Sapienza

et al. 2024

IJMS

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“…En los casos de SUDS (MS inexplicada) en la actualidad se realiza NGS (secuenciación masiva) mediante paneles amplios de genes, que permiten evaluar variantes en genes relacionados con SQT largo, SQT corto, síndrome de Brugada y taquicardia ventricular catecolaminérgica polimórfica, cuyo rendimiento diagnóstico es de 9 a 32%. 31 Los autores no presentan conflicto de intereses al desarrollar el presente manuscrito.…”

Section: Peso Del Corazónunclassified

Análisis clínico e histopatológico de la prevalencia de enfermedades cardiacas en muerte súbita. Estudio en autopsias

et al. 2022

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Introducción: un evento de muerte súbita supone un gran impacto para la sociedad, siendo importante su estudio para aportar conocimiento y fortalecer estrategias de promoción y prevención. Objetivo: determinar la prevalencia de los diagnósticos anatomopatológicos cardiacos definitivos y los hallazgos histopatológicos asociados con la muerte súbita de origen cardíaco en los pacientes sometidos a autopsias clínicas realizadas en el Hospital de San José de Bogotá DC, Colombia, durante el período 2015 a 2018. Métodos: estudio descriptivo de corte transversal retrospectivo en pacientes a quienes se les realizó autopsia con diagnóstico de muerte súbita de origen cardiovascular en el servicio de patología del Hospital de San José, Bogotá DC, Colombia. Resultados: se incluyeron 178 autopsias con diagnóstico de muerte súbita cardíaca. El promedio global de edad fue 56.1 años (DE: 15.06) con una relación hombre-mujer de 3:1. El hallazgo macroscópico más frecuente fue cardiomegalia (promedio 428.1 g (DE 112.8), acompañado de la presencia de coronariopatía esclerótica (p=0.000) con obstrucción de la luz de las arterias coronarias mayores de 80% (p=0.037). Conclusiones: los diagnósticos anatomopatológicos definitivos prevalentes en la muerte súbita cardiaca fueron cardiopatía isquémica crónica complicada (65%) e infarto agudo de miocardio (16%), datos similares a los reportados a nivel mundial. La cardiomegalia es un hallazgo frecuente que debe valorarse en forma cuidadosa.

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“…It was first described in 1763 by Giovanni as arrhythmogenic right ventricular dysplasia, although its official publication occurred in 1982; this was later replaced by arrhythmogenic cardiomyopathy [2]. It is currently recorded in 4% to 7% of sudden deaths (SD) [3]. The way of understanding the disease has changed in parallel with the progression of diagnostic studies, which has caused its definition to vary and is currently based on the sum of imaging, electrocardiographic, histological and genetic/familial variables [4][5][6], updated through the Padua criteria, which include organic involvement of the left ventricle [7].…”

Section: Introductionmentioning

confidence: 99%

New Variant in Placophilin-2 Gene Causing Arrhythmogenic Myocardiopathy

Caimi-Martinez

Antoniutti

Blanco

et al. 2022

Genes

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Introduction: Arrhythmogenic cardiomyopathy (ACM) is an inherited disease characterized by progressive fibroadipose replacement of cardiomyocytes. Its diagnosis is based on imaging, electrocardiographic, histological and genetic/familial criteria. The development of the disease is based mainly on desmosomal genes. Knowledge of the phenotypic expression of each of these genes will help in both diagnosis and prognosis. The objective of this study is to describe the genotype–phenotype association of an unknown PKP2 gene variant in a family diagnosed with ACM. Methods: Clinical and genetic study of a big family carrying the p.Tyr168* variant in the PKP2 gene, in order to demonstrate pathogenicity of this variant, causing ACM. Results: Twenty-two patients (proband and relatives) were evaluated. This variant presented with high arrhythmic load at an early age, but without evidence of structural heart disease after 20 years of follow-up, with low risk in predictive scores. We demonstrate evidence of its pathogenicity. Conclusions: The p.Tyr168* variant in the PKP2 gene causes ACM with a high arrhythmic load and with an absence of structural heart disease. This fact emphasizes the value of knowing the phenotypic expression of each variant.

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

Cited by 11 publications

References 27 publications

Morphological and Genetic Aspects for Post-Mortem Diagnosis of Hypertrophic Cardiomyopathy: A Systematic Review

Morphological and Genetic Aspects for Post-Mortem Diagnosis of Hypertrophic Cardiomyopathy: A Systematic Review

Análisis clínico e histopatológico de la prevalencia de enfermedades cardiacas en muerte súbita. Estudio en autopsias

New Variant in Placophilin-2 Gene Causing Arrhythmogenic Myocardiopathy

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