Neuromuscular diseases represent a group of rare diseases, if individually taken but, if considered as a whole, they constitute a broad category of progressively disabling genetic conditions that require significant assistance efforts both in economic and social impact terms. Given the rarity of some forms, it is not always possible, or even immediate, to recognize the focal genetic cause, with significant consequences on the possibility of carrying out a correct genetic “counseling”.
Thanks to new studies, carried out by means of recent technological advances, in last years there have been many efforts in this regard, and advances in the field of genetics have led to a real explosion in knowledge in these specific fields. In particular, the use in clinical practice - related to rare neuromuscular diseases and conditions with a tricky diagnosis - of new generation sequencing methods (Next Generation Sequencing, NGS) has determined a huge increase in the diagnostic rate, when compared to traditional approaches, prevalently used until a few years ago. At the same time, this innovative approach led to the discovery of multiple genetic mutations, sometimes even in multiple genes at the same time, in turn leading to a widening of clinical phenotypes, often highlighting the lack of an evident correlation between genotype and phenotype.
Such findings also make the general diagnostic picture of the disease more complex, complicating the consequent formulation of rehabilitative plans and of taking care of patients, as well as the possibility that the latter can benefit from tailored genetic treatments.
It is therefore understandable how difficult it can be to extract the role that each genetic variant plays in the phenotypic expressiveness and how the interaction between the different variants can modify the disease progression or the response to treatments. Therefore, the role of a multidisciplinary team of professionals specialized in various fields (clinical geneticists, molecular diagnostics experts, computer scientists, statisticians ...) becomes more and more relevant in the interpretation of these extremely heterogeneous and multiparametric results.
Summarizing, the project aims to simultaneously use different platforms (clinics, bioinformatics, biomechanics ...) in order to make the genotype/phenotype correlation more reliable in a large cohort of patients affected by neuromuscular diseases, studied through new generation techniques, thus helping the clinician in the definition of treatment plans, in monitoring the disease progression and, therefore, in the patients’ care. More specifically, the primary aims of the project include:
The project was officially started on 7 March 2017 and is expected to last 24 months; however, beyond eventual extensions, it can not exceed an overall duration of 30 months.