Emma Walker, United States of America
Washington University Division of Biology and Biomedical SciencesAuthor Of 1 Presentation
DISCOVERY OF A GENETIC VARIANT IN COQ6 PREDISPOSING TO SEVERE CHILDHOOD PNEUMONIA (ID 1080)
Abstract
Background
Severe pneumonia is the major cause of childhood mortality worldwide. Streptococcus pneumoniae remains a leading pathogen in severe acute lower respiratory illness (ALRI) in children globally. Increased incidence of severe ALRI in defined genetic groups suggests heritable components to ALRI susceptibility. We aimed to identify novel susceptibility alleles to severe childhood ALRI.
Methods
In a case-control study, we consented and collected saliva samples from children presenting with ALRI (Cases) and their healthy biological parents or siblings (Controls). Whole exome analysis was performed on 6 children and their controls from Papua New Guinea.
Results
A rare aspartate to tyrosine variant allele of COQ6, COQ6D→Y, was found in a homozygous state in 3 of 6 ALRI cases. The variant was either present in a heterozygous state or absent in controls and enriched above background levels. COQ6 is a required enzyme in ubiquinone biosynthesis. Current work on additional samples seek to validate a genetic association of COQ6D→Y with ALRI.
Conclusions
A novel single nucleotide variant in a ubiquinone biosynthesis enzyme is highly enriched in pediatric populations very susceptible to severe ALRI. Validating COQ6D→Y variant as causative to severe ALRI will inform novel interventional trials using nutritional supplements to treat high risk children, thereby improving ALRI outcomes.