Approved Research

Elucidating the Genetic Landscape of Frontotemporal Dementia (FTD) and Parkinson's Disease (PD)

Lay summary

Frontotemporal Dementia (FTD) and monogenic Parkinson's disease (PD) are the neurodegenerative diseases with the strong genetic link. For example, 40-50% of FTD patients and 10-20% of PD patients report a positive family history. The identification of disease-causing genes has provided critical insights into the underlying FTD and PD pathophysiology. Although several disease-causing genes have been identified for FTD and PD, only 10-40% of patients have known genetic causes. The significant number of FTD and PD patients without known genetic causes warrants further investigation of discovering novel FTD and PD genes.

Whole-exome/genome sequencing (WES/WGS) allows the systematic analyses of genetic variants to identify (rare) causative mutations and to investigate the genetic landscape underlying complex diseases. With a systematic profiling of genetic mutations in our patient cohorts using repeat primed Sanger sequencing and WES/WGS, we aim to describe the frequencies of mutations in the genes that cause neurodegenerative disease and detect the presence of potentially novel pathogenic variants for elucidating important biological pathways to FTD and PD pathogenesis. This project is on-going with more patients being enrolled this year and next year and is expected to go on for the next 12-24 months. By discovering new genetic causes, this could allow diverse presentations of disease to be accurately subdivided into groups of shared genetic causes. Consequently, the efficiency in patients' treatment can be increased. Furthermore, with the identification of the new pathogenic variants, the clinicians can come up with targeted interventions to help patients and their families. This also opens the door to screening and genetic diagnosis.