The First Genetically Confirmed Case of Ataxia with Oculomotor Apraxia Type 1 (AOA1) Due to an APTX Nonsense Variant in a Rwandan Patient: A Case Report

Abstract

INTRODUCTION: Ataxia with oculomotor apraxia type 1 (AOA1) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the APTX gene, which encodes the DNA repair protein aprataxin. The condition is characterized by early-onset progressive cerebellar ataxia, oculomotor apraxia, peripheral neuropathy, and metabolic abnormalities. Despite increasing recognition in Europe and Asia, AOA1 remains underreported in Sub-Saharan Africa due to limited access to advanced genetic diagnostics.

CASE PRESENTATION: We report the clinical and molecular findings of a 10-year-old Rwandan boy who presented with progressive gait instability, dysarthria, developmental delay, and oculomotor apraxia. Neurological examination revealed cerebellar ataxia, dysarthria, muscle weakness, and peripheral neuropathy. Brain magnetic resonance imaging demonstrated cerebellar atrophy with vermis hypoplasia. Genetic analysis, utilizing whole-exome sequencing and an ataxia/spastic paraplegia gene panel, identified a rare homozygous nonsense variant in APTX (NM_001195248.1:c.958C>T; p.Arg320), predicted to result in premature protein truncation and loss of function.

CONCLUSION: This report describes the first genetically confirmed case of AOA1 in Rwanda and, to our knowledge, in Sub-Saharan Africa. The findings expand the geographic and genetic spectrum of AOA1 and highlight the critical importance of integrating genomic diagnostics into clinical practice in under-resourced settings. Improved access to genetic testing is essential for accurate diagnosis, management, and genetic counseling of rare neurogenetic disorders in these regions.