Research findings from the Genomics of Rare Diseases Project presented at Conference

The 59th edition of the European Society of Human Genetics (ESHG) conference took place in Gothenburg, Sweden, from 13 to 16 June. Research conducted within the Department of Applied Biomedical Science, Faculty of Health Sciences, as part of the Genomics of Rare Diseases Project (a UM Research Excellence grant) was presented as a poster showcasing ongoing work on using zebrafish models to characterise a pathogenic mutation giving rise to Lethal Congenital Contracture Syndrome 1 (LCCS1) and Congenital Arthrogryposis with Anterior Horn Cell Disease (CAAHD).

Functional characterisation of the pathogenic GLE1 p.S603 variant using a zebrafish model

LCCS and CAAHD are two autosomal recessive disorders, where the former is fatal in the foetal period while in CAAHD individuals may survive into childhood albeit with significant disability.

Furthermore, survivability in CAAHD depends on both the location of the variant and the availability of early medical intervention. Ms Amy Marie Vella, Prof. Melissa Formosa and Prof. Rosienne Farrugia describe the setting up and characterisation of a zebrafish model to characterise the functional effect of a local founder variant in GLE1.  

This variant uniquely effects the long isoform of GLE1, leaving the short isoform intact. The work presented shows that knocking down a single isoform gives a disease phenotype which is less severe and less lethal increasing survivability, a relevant finding for patients with this mutation.

This work was Ms Vella’s MSc research and was supported by an Endeavour II scholarship (314/2022/79) and the Genomics of Rare Diseases (I21LU04) project awarded to Prof. Farrugia.

The zebrafish facility was set up through projects ZeEBRA (TDP: R&I-2019-018T) and STRONG (TDPLite: R&I-2024-007L) funded by Xjenza Malta and awarded to Prof Formosa. The live stain and confocal microscopy experiments were carried out in collaboration with the European Molecular Biology (EMBL)’s advanced mobile laboratory.

For further information about genomic studies of rare diseases, please contact Prof. Rosienne Farrugia.

For further information about zebrafish research, please contact Prof. Melissa Formosa.