This project is being co-led by Dr. Jordi Diaz-Manera and Dr. Ana Topf and is being done in collaboration with Dr. Rita Barresi and her project titled “Validation of a Blood-Based Assay for Dysferlinopathy in a Latin American Cohort”.
Next generation sequencing (NGS) has revolutionized the diagnostic process of patients with neuromuscular diseases (NMD). However, access to sequencing technologies in less developed regions, such as Latin American countries (LATAM) is not only limited, but also extremely variable. While some countries offer NGS as part of their standard diagnostic pipeline, others still struggle to provide individual gene testing by Sanger Sequencing, leaving their patients genetically undiagnosed.
Latin-SEQ is a newly established consortium of neuromuscular units from LATAM countries with the objective of identifying difficulties in access to genetic testing, and in turn, providing an opportunity for genetic diagnosis to LATAM NMD patients.
Thus, the John Walton Muscular Dystrophy Research Centre (JWMDRC) in collaboration with so far 40 NMD centres participating in the Latin-SEQ consortium has secured funding to perform NGS analysis in 1,000 patients with suspected genetic neuromuscular diseases. Blood, saliva, or DNA samples from NMD patients and their family members will be sent to the JWMDRC in Newcastle, UK, and detailed clinical data will be uploaded in a standardised phenotypic database (PhenoStore). Proband-only exome sequencing will be performed by Centro Nacional the Analisis Geneticos (CNAG) in Barcelona, Spain, and the raw data uploaded to the Genome Phenome Analysis Platform (GPAP, RD-Connect) to be analysed by the research team at the JWMDRC. Genetic variants will be classified following ACMG (American College of Medical Genetics) guidelines, and those with uncertain significance will be individually discussed with the referring centres in periodic multidisciplinary meetings.
Remaining unsolved cases will be subjected to trio exome sequencing with view to identifying novel causative genes and pathomechanisms. In addition, we will study disease prevalence, region-specific genotype-phenotype correlations, founder mutations. This consortium also aims to create an international framework for further collaborative research projects in the region.