Origin of Molecular Genetic Diagnosis in Latin America

In the 1990s, our laboratory initiated the modernization of the diagnosis of Mendelian genetic diseases using molecular biology tools, with the Polymerase Chain Reaction (PCR) as a key method. This review outlines the evolution of the application of these tools for emblematic conditions such as cystic fibrosis, hemophilia A, muscular dystrophies, and growth hormone deficiency. Techniques such as end-point PCR, multiplex PCR, restriction fragment length polymorphisms (RFLPs), probe hybridization, and gene deletion analysis were integrated. In cystic fibrosis, the work transitioned from the initial identification of the ?F508 mutation in the CFTR gene to the use of 16-mutation panels, achieving a regional diagnostic efficacy of 47.9% and documenting the allelic heterogeneity characteristic of Latin American admixture. In muscular dystrophy, multiplex PCR allowed for the discrimination between clinical variants (Duchenne versus Becker) by identifying deletions in hot-spot regions of the dystrophin gene. In hemophilia A, carrier detection via the Bcl I polymorphism was documented, while in the hGH locus, deletions associated with short stature and intrauterine growth restriction were identified. Altogether, these pioneering contributions laid the foundations for clinical molecular genetic diagnosis in the region.