Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected XXXX in infancy and early childhood.

@entity1 @entity1164 @entity296 @entity2333 @entity13192 @entity204
OBJECTIVES: Sudden unexplained @entity204 in @entity1 is a tragic and traumatic event, often worsened when the cause of @entity204 cannot be determined. This work aimed to investigate the presence of putative pathogenic genetic variants in a broad spectrum of @entity296 , @entity13192 and @entity2333 associated genes that may have increased these @entity1 's vulnerability to @entity1164 . DESIGN: We performed molecular autopsy of 41 cases of sudden unexplained @entity204 in @entity1 and @entity1 through massive parallel sequencing of up to 86 @entity1164 -related genes. Multiple in silico analyses were conducted together with a thorough review of the literature in order to prioritise the putative pathogenic variants. RESULTS: A total of 63 variants in 35 cases were validated. The largest proportion of these variants is located within @entity296 genes although this would have been more expected of @entity13192 gene variants. Subtle microscopic features of heart tissue may indicate the presence of an early onset @entity296 as a predisposing condition to sudden unexpected @entity204 in some individuals. CONCLUSIONS: Next-generation sequencing technologies reveal the existence of a wide spectrum of rare and novel genetic variants in sarcomere genes, compared with that of cardiac ion channels, in sudden unexplained @entity204 in @entity1 and @entity1 . Our findings encourage further investigation of the role of early onset @entity296 and other diseases involving @entity296 in these deaths. Early detection of variants in these individuals could help to unmask subtle forms of disease within their relatives, who would eventually benefit from better counselling about their genetic history.
