The 57th edition of the (ESHG) conference took place in Berlin, Germany, from June 1 to 4 June 2024.
Local research being conducted at the University of Malta was presented at the conference in the form of two poster presentations showcasing ongoing work on Idiopathic Hypogonadotropic Hypogonadism (IHH) and Osteoporosis.
These highlight two important studies from the genomics and genetics research groups at the Department of Applied Biomedical Science, , underscoring the impactful work being conducted on a local level.
- Discovering a novel genetic variant in siblings with Idiopathic Hypogonadotropic Hypogonadism (IHH)
IHH is a rare genetic disorder characterised by delayed or absent puberty due to impaired hormone signalling. Mr Clayton John Axiak and Prof. Rosienne Farrugia, together with co-authors from the UM (Ms Francesca Borg Carbott, Dr Ritienne Attard, Dr Karen Cassar, Dr Mark Gruppetta, Prof. Josanne Vassallo and and the identified a novel in-frame deletion mutation in the KISS1R gene in two Maltese individuals with IHH.
Functional KISS1R is crucial for reproductive health. Functional studies of the variant, KISS1R p.Y190_A199del, using bioluminescence resonance energy transfer and homogeneous time-resolved fluorescence assays, confirmed that this genetic variant significantly impaired receptor signalling in transfected HEK293 cells after metastin stimulation. These findings enhance our understanding of the genetic basis of IHH and provide potential new avenues for diagnosis and treatment.
- Identification of Structural Variants (SVs) underlying Familial Osteoporosis
Ms Azra Zejnelagic, Ms Chanelle Cilia, Prof Josanne Vassallo, Prof Jean-Paul Ebejer, and Prof Melissa Formosa presented their research on the role of SVs in the genetic of osteoporosis – a metabolic bone disorder characterised by low bone mass and strength, increasing fracture risk. The study aimed to identify SVs as possible bone mass determinants using whole genome sequencing data generated from a Maltese family having several relatives affected with osteoporosis.
Several affected relatives from a two-generation Maltese pedigree were subjected to whole genome sequencing. The team employed three different tools for SV detection and calling, including BreakDancer, Lumpy, and Pindel. Comprehensive variant filtering following a dominant inheritance pattern identified three validated SVs within the ARHGEF3, TBX15, and ADAM9 genes in the Lumpy output, whereas SVs in SOD2 and KLF12, were identified by Pindel. No variants were shortlisted by BreakDancer. The findings suggest that the identified SVs could act as possible genetic determinants of bone mass and could serve as targets for future therapeutic interventions for osteoporosis.
The IHH study received funding from the Malta NGS project (R&I-2012-024) financed by the Malta Council for Science and Technology, The Genomics of Rare Diseases project (I21LU04), a University of Malta Research Excellence Grant, and a Trialect Traineeship.
The osteoporosis study is supported by the GRIT project (R&I-2022-007L) financed by the Malta Council for Science and Technology, for and behalf of the Foundation for Science and Technology, through the FUSION R&I Technology Development Programme Lite.
