251P Latin-SEQ: a collaborative network to provide genetic diagnosis to patients with neuromuscular diseases in Latin America – project update

• Published in: Neuromuscular disorders : NMD Vol. 43; p. 104441
• Main Authors: Topf, A., Gonzalez-Chamorro, A., Laurie, S., Ntalis, A. Papakonstantinou, Consortium, Latin SEQ, Diaz-Manera, J.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-10-2024
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2024.07.468

Next generation sequencing has revolutionized the diagnostic process of patients with neuromuscular diseases. However, access to these technologies in less developed regions, such as Latin America (LatAm) is still limited, leaving many patients genetically undiagnosed. In the past year, Latin-SEQ, a consortium of clinical centres specialising in neuromuscular diseases across all LatAm, was established with the objective of identifying challenges in accessing genetic testing, and in turn providing an opportunity for genetic diagnosis to LatAm patients. The Latin-SEQ consortium comprises more than 50 centres from 29 cities in 18 LatAm countries so far. Patients and family members are currently being recruited into the study, and a total of 356 biological samples have been collected, including from 191 affected individuals. Detailed phenotypic data has been uploaded in an HPO-based clinical database (PhenoStore). The most frequent clinical diagnosis is unspecified myopathy (21%), followed by neuropathy (17%), congenital myopathy (8.5%), metabolic myopathy (8.5%) and limb girdle muscular dystrophy (8%). Patients where Duchenne/Becker or SMA is suspected are first tested by MLPA. If negative, probands undergo exome sequencing (CNAG, Spain), and data is uploaded to the Genome-Phenome Analysis Platform (GPAP) for analysis and interpretation. As of April 2024, five patients have a confirmed SMA diagnosis (out of 8 tested, 62.5%) and in a further nine (out of 20, 45%), candidate disease-causing variants in ANO5, FLNC, ACTA1, RYR1, DMD, LPIN1 and LMNA have been identified. Proposed genetic diagnoses will be discussed with the referring centres during interdisciplinary meetings. Analysis is ongoing. In addition, Latin-SEQ will help understand disease prevalence and identify founder mutations and region-specific genotype-phenotype correlations. Lastly, this consortium aims to create an international framework for further collaborative research projects in the region.