Universität zu Köln

Santori, Montserrat ORCID: 0000-0002-7721-1194, Blanco-Verea, Alejandro, Gil, Rocio ORCID: 0000-0002-8522-7436, Cortis, Judith, Becker, Katrin, Schneider, Peter M. ORCID: 0000-0003-0744-2349, Carracedo, Angel ORCID: 0000-0003-1085-8986 and Brion, Maria ORCID: 0000-0001-7463-2148 (2015). Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood. Arch. Dis. Child., 100 (10). S. 952 - 957. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2044

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Santori, Montserrat UNSPECIFIED orcid.org/0000-0002-7721-1194 UNSPECIFIED Blanco-Verea, Alejandro UNSPECIFIED UNSPECIFIED UNSPECIFIED Gil, Rocio UNSPECIFIED orcid.org/0000-0002-8522-7436 UNSPECIFIED Cortis, Judith UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Peter M. UNSPECIFIED orcid.org/0000-0003-0744-2349 UNSPECIFIED Carracedo, Angel UNSPECIFIED orcid.org/0000-0003-1085-8986 UNSPECIFIED Brion, Maria UNSPECIFIED orcid.org/0000-0001-7463-2148 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-391626
DOI:	10.1136/archdischild-2015-308200
Journal or Publication Title:	Arch. Dis. Child.
Volume:	100
Number:	10
Page Range:	S. 952 - 957
Date:	2015
Publisher:	BMJ PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1468-2044
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SARCOMERIC GENE-MUTATIONS; REGULATORY LIGHT-CHAINS; HYPERTROPHIC CARDIOMYOPATHY; MYOSIN; MYOPATHY; VARIANTS; CHILDREN; THICK Multiple languages Pediatrics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39162