Characterization of TSEN54 function in human brain development and in pontocerebellar hypoplasia

01.04.2021 bis 31.03.2022

Pontocerebellar hypoplasia (PCH) is a group of extremely rare, neurodegenerative disorders with fetal onset that impairs the development of the cerebellum and ventral pons. About 90 % of the affected patients carry a homozygous missense mutation (p.A307S) in the TSEN54 gene. Despite the severe impact on patients diagnosed with PCH2A and their families, little is known about the exact cellular and molecular pathological mechanisms of PCH2A. We aim to use different neural organoids as model systems to identify the cellular and molecular function of TSEN54 in human cerebellar and neocortical development. A better understanding of the molecular pathways involved in this disease is important to define biomarkers for early diagnosis, and ultimately develop treatment strategies that could be implemented on neonates carrying a TSEN54 mutation.