The p.Gly2019Ser is the commonest pathogenic mutation in the LRRK2 gene among Egyptians with familial and sporadic Parkinson's disease

Abstract

<title>Abstract</title> The impact of <italic>LRRK2</italic> variants on the risk of Parkinson's disease (PD) in Egyptians remains unknown. We examined 1,210 Egyptians (611 PD patients and 599 controls) for 12 <italic>LRRK2</italic> mutations. The p.Gly2019Ser was the only variant detected across Egypt, with a prevalence of 4.1% in sporadic cases, 6.5% in familial cases, and 0.68% in controls. Among p.Gly2019Ser carriers, all were heterozygous bar one homozygous patient, and all shared the common haplotype 1. Demographics and UPDRS scores did not differ between carriers and non-carriers, with most patients being males and developed PD in their fifties. Early-onset PD prevalence was 33% in carriers and 25% in non-carriers. Familial cases were 16% in carriers and 11% in non-carriers. This study affirms that like other North Africans and Mediterranean populations, Egyptians with PD have a notably high prevalence of the p.Gly2019Ser. <italic>LRRK2</italic> inhibitors could be promising therapeutic options for further exploration in this population.