Genetic insights into ataxia with ocular apraxia type 1: Unraveling a mutation in APTX in a case report of Pakistani family

Ataxia with oculomotor apraxia type 1 (AOA1) is an uncommon genetic condition characterized by dysarthria and gait abnormalities. The predominant characteristic of AOA1 is childhood-onset progressive cerebellar ataxia. Our study aimed to determine the clinical and molecular spectrum of AOA1. We investigated a consanguineous Pakistani family with four affected individuals with early-onset progressive ataxia by using whole-exome sequencing (WES) and co-segregation analysis. Sequencing analysis revealed a novel homozygous variant c.527 T > G (p.Val176Gly) in exon 5 of the aprataxin ( APTX) gene. The prominent clinical features of affected individuals include wide-based ataxic gait, difficulties walking, dysmetria, and limb ataxia. The findings of this study broaden the genotypic spectrum of APTX mutations. • Ataxia with ocular apraxia type 1 (AOA1) exhibits clinical heterogeneity in a Pakistani family. • The mutations in aprataxin gene (APTX), located on chromosome 9p13, are considered as causative factor of AOA1. • The mutation c.527 T > G (p.Val176Gly) in APTX is located inside an HIT domain. • The research offers an indicator to investigate the hidden mutations in Pakistani community. • This study increased the mutation spectrum of APTX globally.