Whole genome sequencing characterisation of paediatric cardiomyopathy: toward precision medicine

Paediatric cardiomyopathies are serious disorders affecting the heart muscle and the leading cause of heart transplant in children. Although rare (1:100,000)the morbidity, mortality and burden on the NHS are high. A genetic diagnosis is critical for individualised management and improved outcomes.

There is a significant genetic component yet sequencing known cardiomyopathy-associated genes can identify a genetic cause in less than half of cases.

It is likely that a large portion of the remaining unexplained cases are also genetic in origin, caused by as yet uncharacterised genes or variant types, representing enormous opportunity to achieve diagnoses for families and advance our understanding of fundamental disease biology.

In this fellowship I will leverage access to unique, well phenotyped, rare-disease cohorts and scientific expertise to undertake a cutting-edge gene hunting programme.

I will analyse whole genome sequencing data, including underexplored regions and variant types, from children and their parents to identify novel disease genes and variants.

In responding to this unmet need to achieve diagnoses and better understand biology underlying paediatric cardiomyopathy, I will also seek to address two important questions for genomic medicine as a whole: where is the missing heritability, and how can we distinguish benign from pathogenic genetic variation?