Abstract
Next generation sequencing (NGS) based tests have become first-line investigative modalities in adult neurogenetic clinics. Studies in high-income countries (HICs) show that NGS is cost-effective and reliable in diagnosing adult neurogenetic disorders (NGDs). African populations harbour vast genomic diversity, but there is limited knowledge on the molecular basis of NGDs affecting these populations due to lack of access to the necessary technology. The primary objective of this retrospective study was to describe the clinical utility of NGS panels in an African low-middle income country (LMIC). It included data of 74 adult participants seen at the multidisciplinary neurogenetic clinic at Tygerberg Hospital, South Africa, over a 4 - year period. Forty-three symptomatic index cases underwent NGS panel testing, while 31 relatives received targeted familial variant testing based on specific indications relevant to each case. Twenty-two different disease group-specific NGS panels were requested, spanning the NGD phenotypic spectrum. The diagnostic yield (DY) in index cases was 39.5% (17/43). Four relatives were clinically affected, and all tested positive for the familial-specific variant. This study demonstrated the DY achieved with NGS testing in an LMIC adult neurogenetic cohort, was comparable to DYs previously reported in HICs. These results argue for the use of NGS panels as first-tier testing in resource constrained LMICs, to limit lengthy diagnostic odysseys and unnecessary investigations. A definitive molecular diagnosis enables evidence-based management, surveillance, genetic counselling, and familial variant screening for relatives. Lastly, it assists with enrolment into clinical trials focussed on the development of precision medicine.