1. Genotype-Phenotype correlations in Marfan syndrome. The AIMS trial on Marfan syndrome patients is allowing us to study the effect of the drug on each particular mutation. We are working on the creation of an AIMS-UK group to study the genotype (mutation found) versus the phenotype (clinical fetures) in each patient to observe any differences between the placebo and the drug. This will refine the significance of the AIMS trial findings, and possibly the creation of an international consortium where we will be able to study samples around the world on other trials on the Losartan drug and compare mutations between drugs and placebo to better understand the effect of the drug on the patient.
2. Mapping the Marfan gene. We have a large Marfan syndrome database which contains mutations from samples that have variability in their clinical features. We are studying families with the same mutation (or similar mutation) to clarify the consequence of each mutation, and therefore in the future, we will be able to predict the different clinical features and arrange a better and healthier management of the condition.
We are still collaborating with a research group led by Dr. Sinha in Cambridge, UK, where we are studying multiple drugs within cultured cells from Marfan syndrome patients. This study is very important since it is a great opportunity for the Marfan syndrome community to test different drugs at a time when it could be very expensive to arrange a clinical project of such proportions.
3. Novel genes for dislocated lens phenotype – Ectopia Lentis (EL). We are creating an international consortium of ophthalmologists based in London at the Guy Scadding Building (Marfan Trust) with the involvement of Dr. Aman Chandra (a very good friend of the Sonalee Lab and a continuous collaborator to the study of EL) to pursue a better understanding of this phenotype found in Marfan syndrome. So far, two proteins (FBN1 and ADAMTL4) are involved in EL but the Sonalee Laboratory has been creating an EL database where the genetic involvement is unknown. Understanding the genetic involvement of different proteins in EL can help differentiate overlapping conditions from Marfan syndrome.
4. Novel genes for hypermobility Ehlers-Danlos syndrome (hEDS). There are 4 common types of Ehlers-Danlos syndrome that we know, and type 4 (vEDS which involves the cardiovascular system – aneurysms and dissections of the aorta) is the most fatal one. We are working with families with a type of EDS involving hypermobile joints (hEDS) for which a gene has not been found yet. We intend to find the gene/genes from hEDS families and to better understand this type of connective tissue disorder as well as the involvement of these genes in the rest of the connective tissue disorders’ family.
5. Novel genes for familial thoracic aortic aneurysm and dissection phenotype (FTAAD). The main phenotype found in Marfan syndrome is TAAD. When it is inherited it is called familial TAAD (FTAAD). We know from networking at international meetings that the group of genes involved in TAAD has been enlarging rapidly in recent years. The structure, composition and maintenance of the aorta is obviously very complicated. There must be many more genes involved in the aneurysm phenotype since we have a cohort of patients (70%) with no gene identified as yet.
Sonalee Laboratory Wish List
This project list above reflects the studies we’re working on, but not the amount of work behind it. In order to keep up with the work that Marfan Trust is investing in the Sonalee Lab, we need to finance some full time expert help. In the meantime medical students can be taken on staff to learn about Marfan Syndrome during a summer project.
Summer Student Projects
Some of the jobs that need doing in the Lab to further our projects include:
• Family pedigree drawing and storage in a format that can be easy to update and keep electronically.
• Adding phenotype (clinical features) of each patient in a database.
• PCR, variant analysis and interpretation on the different projects.
Ideally we would have a technician for each job, but just to have one technician is now a HUGE necessity. This is because it is vital that the Sonalee Lab gets fully up to speed on the recent scientific advancements of the last few years. e.g. Next Generation Sequencing (NGS) is fairly new and we have a lot to learn about the manipulation of the data created, however, to further our research it is crucial that we also keep on top rapidly evolving scientific developments.
To help us with these projects, we badly need donations to cover the following:
1. Three named summer studentships at £1,000 each for 6 weeks project. The donor has an opportunity to add their name or a family member’s name to the studentship.
2. A laboratory technician educated at least to BSc level in a related subject. Salary Scale Grade Level-1a (£21,570 for the first year). Funding for subsequent years will be sought from other sources.
Please, please help us get the Sonalee Lab up and running with the help in needs ASAP by donating in any of the ways detailed in our donate page
Dr José Antonio Aragon-Martin, Director, Sonalee Laboratory