Clinical exome sequencing elucidates underlying cause of death in sudden unexpected death of infants: two case reports

AbstractSudden unexpected death in infants (SUDI) is a traumatic event for families, and unfortunately its occurrence remains high in many parts of the world. Whilst cause of death is resolved for most cases, others remain undetermined following postmortem investigations. There has been a recognition of the role of genetic testing in unexplained cases, where previous studies have demonstrated the resolution of cases through DNA analyses. Here we present two case reports of SUDI cases admitted to Salt River Mortuary, South Africa, and show that underlying causes of death were determined for both infants using clinical exome sequencing. The first infant was heterozygous for a variant (rs148175795) inCOL6A3, which suggested a bronchopulmonary dysplasia phenotype. This hypothesis led to finding of a second candidate variant inDMP1 (rs142880465), which may contribute towards a digenic/polygenic mechanism of a more severe phenotype. Histological analysis of retained tissue sections showed an asphyxial mechanism of death, where bronchiolar muscle weakness from an underlying bronchopulmonary dysplasia may have contributed to the asphyxia by affecting respiration. In the second infant, a homozygous variant (rs201340753) was identified inMASP1, which was heterozygous in each parent, highlighting the value of including parental DNA in genetic studies. Whilst mannose-binding lectin deficiency could not be assessed, it is plausible that this variant may have acted in combination with othe...
Source: International Journal of Legal Medicine - Category: Medical Law Source Type: research