Rare Disease Day is the globally-coordinated movement on rare diseases, working towards equity in social opportunity, healthcare, and access to diagnosis and therapies for people living with a rare disease.
Research at UM
Genomics, through the use of high throughput sequencing has revolutionised the fields of genetic research and genetic diagnostics through faster, cheaper and more accurate testing methodologies. It has also enabled the study of rare diseases which could not be elucidated with traditional methods. Rare disease research is a priority research area for the EU because even though a rare disease only affects less than one in 2000 people, cumulatively rare diseases affect around 30 million people in the EU alone.
The Genomics of Rare Diseases project is funded through a Research Excellence Grant of the University of Malta and led by Dr Rosienne Farrugia, Head of Department of Applied Biomedical Science. High throughput sequencing is being used to identify the underlying genetic causes of a number of conditions prevalent in the Maltese population to enable the development of new diagnostic tests and therapies. “In high throughput sequencing, we take the DNA of an individual, break it up into small pieces and ‘read’ those pieces. Then using bioinformatic pipelines we put the entire sequence back together and identify the places where there is a DNA change that can explain the disease. These findings can then be used in diagnostic tests.” said Dr Farrugia.
“The diseases we are actively studying include polycystic kidney disease, Hirschsprung disease, idiopathic hypogonadotropic hypogonadism and the tetrahydrobiopterin deficiencies. A number of undergraduate and postgraduate students are contributing to this work and key findings have been presented at the European Society of Human Genetics meeting and the meeting of the American Society of Human Genetics.” She continued.
Further details of the study can be found on THINK’s website.
The role of Genetic counsellors
As genetic counsellors (GCs), their role in the diagnosis and management of rare diseases is multi-faceted. Firstly, they support patients through the journey of genetic testing. In the case where a genetic change is found, provide psychosocial support, and work together with individual patients and their families to help them adapt and adjust to the genetic diagnosis.
Additionally, they also identify other family members who may be at risk of having or passing on a condition, help the patient to understand the genetics of the condition by simplifying the science and providing explanations in layman’s terms. Furthermore, the GCs explore the implications of genetic test results and signpost patients to screening and/or treatment services to manage the condition.
A rare disease - Genomics of developmental globin gene expression in Thalassaemia
The long-term objective of thalassaemia research is to determine the mechanisms of the perinatal transition from foetal to adult haemoglobin biosynthesis and the reverse switching of the globin gene for treating Haemoglobinopathies (Hbpy).
KLF 1 is an erythroid transcriptional factor that is thought to be the master regulator of erythropoiesis, and a regulator in the γ- to β-globin gene switching. A variant of this gene could lead to increased foetal haemoglobin as the variant gene prevents the switching of gamma chains in the foetal haemoglobin to the beta chains in adult haemoglobin. This makes its presence in beta thalassaemia patients beneficial, as the foetal haemoglobin compensates for the damaged beta chains. β-thalassaemia arises from a decreased or absence of the synthesis of the beta globin, resulting from single nucleotide substitutions, deletions, or insertions of oligonucleotides which lead to frameshift mutations. Beta thalassaemia can also arise from gross deletions of the beta globin gene on chromosome 11.
The reactivation of silenced alpha and beta globin loci genes may offer therapeutic opportunities to individuals with abnormal production of the Beta globin chains. The substitution of the beta globin chains with the foetal globin chains may be able to reverse the effects of thalassaemia through the production of normal HbF. Reverse phase HPLC allows for the separation of the globin into their different components, allowing for the ability to distinguish between variants, and Gene Sequencing methods are used for the identification of variations in the genes, indicating the condition of an individual and explaining the clinical observations.
Message from the Directorate for Health and Research
Miriam Azzopardi, a consultant in Public Health stated that “The Rare Disease Register in Malta is a population-based register established about 10 years ago within the Directorate for Health and Research. The initial main sources of information were the Malta National Cancer Registry, the Malta National Congenital Anomalies Register and the List of Patients referred abroad for treatment of Rare Diseases. The database's IT structure was changed in 2020 so that the register could systematically pick up information from the above-mentioned registers and could also access the Mater Dei"s IT systems for the verification of cases. Further data sources were added, including data coming from clinical databases, etc. The Rare Disease Register now can be considered a useful tool for providing data to policy makers and providing a picture of the Rare Diseases present in Malta and their burden.”
