A decade of whole-exome sequencing in Brazilian Neurology: from past insights to future perspectives

Abstract

Over the last decade, whole-exome sequencing (WES) has become a standard diagnostic tool, significantly transforming the landscape of clinical genetics and playing a pivotal role in the diagnosis of neurogenetic diseases. This revolutionary shift has left a lasting impact on the field of neurology in Brazil. The current review article examines key developments and milestones achieved in Brazil through the application of WES in neurology and discusses forthcoming challenges and essential steps to advance molecular diagnosis. Several studies report the use of WES to diagnose genetic disorders with neurological manifestations in Brazil, underscoring the growing importance of molecular diagnosis in neurogenetics. These studies often provide detailed phenotypic analyses and clinical descriptions, offering valuable insights into the genetic underpinnings of several neurological conditions. Many reports highlight the use of WES in the investigation of complex neurological conditions in Brazil, such as neurodevelopmental disorders, hereditary spastic paraplegia, movement disorders, and ataxia. The discovery of new genes implicated in monogenic diseases with neurological manifestations through WES was a significant breakthrough. Despite these advances, the availability of large cohort studies on rare diseases in Brazil remains limited, hindering the ability to generalize findings and explore the full spectrum of genetic diversity. However, a few larger cohort studies have substantially contributed to our understanding of rare diseases and specific neurological disorders.While WES has limitations and may eventually be supplanted by more advanced diagnostic tools, it left a permanent mark on the neurology field in Brazil. The field of neurogenetics is set to become increasingly important in the future.

Figure 1

Schematic figure of the gene, including the non-coding elements (enhancer/silencer and promoter), introns, and exons. Exons correspond to the coding part of the gene that is translated to a protein; they correspond to approximately 2% of the genome, but cause most of the known genetic disorders. Whole-exome sequencing (WES) can only identify variants in the exons. Whole-genome sequencing (WGS) can identify variants in any part of the genome, including the non-coding DNA.