RNA-protein interactions. Defective RNA processing and neurodegeneration. Genetic disease caused by defective splicing.
The ICGEB Trieste Molecular Pathology Group has collaborated on a study which has brought to light a previously unknown neuro-developmental disorder caused by mutations in SF3B3, a key component of the RNA splicing machinery.
Published in a recent report in the journal Genome Medicine, the condition spans a broad clinical spectrum – from severe prenatal cases to milder forms marked by autism and developmental delay. The study was initiated by the work of doctor Luciana Musante at the Burlo Garofolo Children’s Hospital in Trieste and Prof. Flavio Faletra from the ASUFC Institute for Medical Genetics and the University of Udine, with the collaboration of the Molecular Pathology Group at ICGEB Trieste, headed by ICGEB Scientific Coordinator Dr. Emanuele Buratti.
The contribution of ICGEB scientists has played an important role in better characterising the widespread disruption of gene regulation. In particular, the RNA sequencing performed by Dr. Buratti’s Lab has revealed hundreds of misregulated genes, with the strongest effects on pathways controlling the cell cycle and early development, including heart formation and neurogenesis.
Crucially, many of these altered genes are already linked to human disease, thus helping explain the complex, multisystem symptoms seen in patients. The findings also connect these molecular changes to real developmental processes. For example, by comparing patient data with fetal heart datasets, researchers found significant overlap with genes active during human heart development, providing a direct link to the frequent cardiac defects observed.
Overall, the study shows how defects in a core splicing factor can ripple across the genome, disrupting critical developmental programmes and giving rise to a new class of genetic disease.
