BRIDGE- EDS (Ehlers-Danlos Syndrome)

Summary

Ehlers-Danlos Syndrome (EDS) is a rare Mendelian disorder of the connective tissue which remain largely uncharacterised genetically. We have a large existing collection of cases, covering the whole spectrum of the syndrome. Using target enrichment and next-generation sequencing (NGS), we have already screened these samples for those variants know to be associated with the condition, however, the majority (>70%) remain unclassified. This project proposed that cases without a present molecular diagnosis should be further characterised by exome sequencing. The work stands to redefine the molecular genetic architecture of the condition, potentially identifying n ew susceptibility genes and thereby increasing the proportion of patients to whom a molecular genetic diagnosis can be attributed. Around 180 exomes have been sequenced from previously uncharacterised patients with EDS and the exomes have now undergone full analysis of variants in known and candidate EDS genes by the study team including Aitman, Weerakkody, Vandrovcova and Vandersteen. Some of the original data from whole genome sequencing from separate patients in the EDS cohort have already been published in the flagship BRIDGE publication. We now request permission to carry out a full burden analysis on the exome sequence data in collaboration with Professor Cordell of the University of Newcastle. The new work will be used to estimate the effects of SNPs within known and suspected EDS genes for a further publication.