Developing a Pipeline to Employ RNA-Seq as a Complementary Diagnostic Tool in Rare Diseases

What this Trial Is About

Researchers are exploring how RNA sequencing (RNA-Seq) can help diagnose rare genetic diseases in children and adults who show early symptoms but have negative results from previous DNA tests called whole-exome sequencing (WES). This project aims to set up and validate RNA-Seq techniques using healthy volunteers and patients with known genetic changes affecting RNA. The study focuses on identifying RNA changes in skin cells and comparing these to blood samples to better understand diseases that are hard to diagnose. Participants include healthy adults, patients with diagnosed genetic diseases affecting RNA, and undiagnosed patients suspected of having rare genetic conditions. Skin biopsies will be taken to culture fibroblasts, which are then analyzed using RNA-Seq to detect RNA level and splicing alterations. Blood samples will also be collected to study genetic and RNA changes. The study includes a discovery group with patients whose WES results were inconclusive, aiming to use RNA-Seq as an additional diagnostic tool. Participants will undergo skin biopsies and blood collection, and their samples will be stored in a biobank for analysis. Researchers will assess RNA changes in fibroblasts and compare RNA profiles from skin and blood. The main outcomes measure the setup and validation of RNA analysis methods and the detection of RNA alterations in patients. Participants will provide consent before enrollment, and their involvement includes sample collection and clinical information gathering. The study is expected to continue through June 2026.

Developing a Pipeline to Employ RNA-Seq as a Complementary Diagnostic Tool in Rare Diseases