Methodological advances in patient-centered rare disease research: the UTHealth Houston Turner Syndrome Society of the United States research registry.

BACKGROUND: Many different clinical specialists provide care to patients with Turner syndrome (TS), who have highly variable clinical manifestations. Therefore, a national TS registry is essential to inform a cohesive approach to healthcare and research. In 2015, the Turner Syndrome Society of the United States (TSSUS) created the Turner Syndrome Research Registry (TSRR) to engage directly with community participants who voluntarily provide longitudinal data about their experiences with TS. TSRR projects are collaborative partnerships between people with TS, TSSUS, and researchers. RESULTS: To ensure that registry workflows conform to the data privacy choices of participants, TSSUS collaborated with UTHealth Houston in 2021 to create a new version of the TSRR that completely separates participant health data (stored at UTHealth) and personal identifiers (maintained at TSSUS). We developed an innovative Visual Basic (VB) script that, when embedded into Microsoft Outlook, redirects REDCap surveys through TSSUS to participants by matching registry IDs to participant email addresses. Additionally, the utilization of REDCap allows for portability of data as it is an open source platform. CONCLUSION: In this report, we will highlight three recent changes that more closely align the TSRR with this mission: a unique and equal collaborative partnership between UTHealth and TSSUS, an open-source platform, REDCap, that ensures data portability and compatibility across institutions, and an innovative survey routing system that retains participant confidentiality without sacrificing REDCap survey distribution capabilities to connect researchers with thousands of participants.

Whole Exome Sequencing Uncovers the Genetic Complexity of Bicuspid Aortic Valve in Families with Early Onset Complications.

Bicuspid Aortic Valve (BAV) is the most common adult congenital heart lesion with an estimated population prevalence of 1%. We hypothesize that early onset complications of BAV (EBAV) are driven by specific impactful genetic variants. We analyzed whole exome sequences (WES) to identify rare coding variants that contribute to BAV disease in 215 EBAV families. Predicted pathogenic variants of causal genes were present in 111 EBAV families (51% of total), including genes that cause BAV (8%) or heritable thoracic aortic disease (HTAD, 17%). After appropriate filtration, we also identified 93 variants in 26 novel genes that are associated with autosomal dominant congenital heart phenotypes, including recurrent deleterious variation of FBN2, MYH6, channelopathy genes, and type 1 and 5 collagen genes. These findings confirm our hypothesis that unique rare genetic variants contribute to early onset complications of BAV disease.