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Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood
  1. Montserrat Santori1,2,3,
  2. Alejandro Blanco-Verea1,2,3,
  3. Rocio Gil1,2,3,
  4. Judith Cortis4,
  5. Katrin Becker4,
  6. Peter M Schneider4,
  7. Angel Carracedo2,3,5,
  8. Maria Brion1,2,3
  1. 1Xenética de Enfermidades Cardiovasculares, Instituto de Investigación Sanitaria de Santiago, Red de Investigación Cardiovascular (RIC), Santiago De Compostela, Spain
  2. 2Grupo de Medicina Xenómica, University of Santiago de Compostela, Santiago de Compostela, Spain
  3. 3Fundación Pública Galega de Medicina Xenómica, SERGAS, Santiago de Compostela, Spain
  4. 4Faculty of Medicine, Institute of Legal Medicine, University of Cologne, Cologne, Germany
  5. 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University Jeddah, Kingdom of Saudi Arabia
  1. Correspondence to Dr Maria Brion, Hospital Clínico Universitario de Santiago, Edificio de Consultas—Planta-2, Laboratorio 1 (IDIS), Travesa da Choupana s/n. Santiago de Compostela CP 15706, Spain; maria.brion{at}


Objectives Sudden unexplained death in children is a tragic and traumatic event, often worsened when the cause of death cannot be determined. This work aimed to investigate the presence of putative pathogenic genetic variants in a broad spectrum of cardiomyopathy, channelopathy and aortic disease associated genes that may have increased these children's vulnerability to sudden cardiac death.

Design We performed molecular autopsy of 41 cases of sudden unexplained death in infants and children through massive parallel sequencing of up to 86 sudden cardiac death-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 cardiomyopathy genes although this would have been more expected of channelopathy gene variants. Subtle microscopic features of heart tissue may indicate the presence of an early onset cardiomyopathy as a predisposing condition to sudden unexpected death 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 death in infants and children. Our findings encourage further investigation of the role of early onset inherited cardiomyopathies and other diseases involving myocardial dysfunction 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.

  • Genetics
  • SIDS

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