Implementation and clinical utility of transcriptome sequencing by RNA-seq in EBCompleted
|Project lead||Dr. Jouni Uitto|
|Organisation||Thomas Jefferson University, Jefferson Medical College|
|Project budget||USD 195,754.00|
|Start date / Duration||01. Dec 2016 / 24 months|
|Funder(s) / Co-Funder(s)||DEBRA Austria, MSAP/EBEP Reviewed|
|Research area||EB genetics, epigenetics & biology|
Short lay summary
EB is a group of genetic diseases where mutations in different genes result in blistering and fragility of the skin and mucous membranes. Identification of the mutated genes and the specific type of mutations in each individual patient is critical for proper subclassification of the disease, and it is helpful for predicting the severity of the disease early on during childhood. Knowledge of the specific mutation is also required for the application of some new therapies that are currently being developed for the treatment of patients with specific types of mutations. Thus, knowledge of the individual’s mutation is critical for the application of appropriate therapies.
The strategies used for mutation detection at this point are only partially (80%) effective, and many of the patients do not know their specific mutations. Furthermore, the knowledge of certain types of mutations is suggestive but does not confirm, of the consequences of the mutations. In this study, we propose a new strategy, which will increase the yield of mutations and their specific consequences.
The patients participating in this study may be asked to give a small skin biopsy (~3-4 mm in diameter). This biopsy, which is done under local anaesthesia, carries a small risk of pain and infection which, however, can be treated by pain killers and appropriate antibiotic therapy.
Identification of specific types of mutations in a gene is the prerequisite for the development of new treatments of precision medicine for EB. The currently proposed work, which will identify specific mutations in affected individuals, is a prerequisite for applying the actual treatments to an individual patient. It is unclear at this point as to how long it will take before such treatments will be available to the patients.
The risks of identifying the mutations, as proposed in this study, are minimal and relate to the skin biopsy (see above).
We estimate that 50 patients with different forms of EB will be enrolled in the study. All patients with an established diagnosis of EB are potentially eligible for the study.
As there is currently no specific or effective treatment for EB, any of the ongoing developments of precision medicine approaches based on the knowledge specific types of mutations would be an advance to the subgroup of patients with such a specific mutation.