The p.Gly2019Ser is a common LRRK2 pathogenic variant among Egyptians with familial and sporadic Parkinson's disease

Martina B William; Sharifa Hamed; Ali Shalash; Eman M Khedr; Mohamed H Yousef; Shaimaa El-Jaafary; Gharib Fawi; Asmaa Helmy; Eman Hamid; Mohamed Essam; Hamin Lee; Alina Jama; Mohamed Koraym; Doaa M Mahmoud; Sara Elfarrash; Yasmin Elsaid; Asmaa S Gabr; Nourhan Shebl; Nesreen Abdelwahhab; Tamer M Belal; Nehal A B Elsayed; Mohamed El-Gamal; Shimaa Elgamal; Salma Ragab; Jaidaa Mekky; Lobna Aly; Samir Nabhan; Gaafar Ragab; Mohamed A Hussein; Mohamed Tharwat Hegazy; Henry Houlden; Mohamed Salama; Mie Rizig

doi:10.1038/s41531-024-00826-8

The p.Gly2019Ser is a common LRRK2 pathogenic variant among Egyptians with familial and sporadic Parkinson's disease

NPJ Parkinsons Dis. 2024 Nov 6;10(1):215. doi: 10.1038/s41531-024-00826-8.

Authors

Martina B William^{1

2}, Sharifa Hamed³, Ali Shalash⁴, Eman M Khedr³, Mohamed H Yousef¹, Shaimaa El-Jaafary⁵, Gharib Fawi⁶, Asmaa Helmy⁴, Eman Hamid⁴, Mohamed Essam⁴, Hamin Lee⁷, Alina Jama⁷, Mohamed Koraym³, Doaa M Mahmoud³, Sara Elfarrash⁸, Yasmin Elsaid⁹, Asmaa S Gabr¹, Nourhan Shebl¹, Nesreen Abdelwahhab⁹, Tamer M Belal⁹, Nehal A B Elsayed¹⁰, Mohamed El-Gamal¹¹, Shimaa Elgamal¹², Salma Ragab¹², Jaidaa Mekky¹³, Lobna Aly¹³, Samir Nabhan¹, Gaafar Ragab^{14

15}, Mohamed A Hussein¹⁴, Mohamed Tharwat Hegazy^{14

15}, Henry Houlden⁷, Mohamed Salama^{16

17}, Mie Rizig¹⁸

Affiliations

¹ Institute of Global Health and Human Ecology, The American University in Cairo, Cairo, Egypt.
² Department of Clinical Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
³ Department of Neurology, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁴ Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
⁵ Department of Neurology, Faculty of Medicine, Cairo University, Cairo, Egypt.
⁶ Department of Neurology, Faculty of Medicine, Sohag University, Sohag, Egypt.
⁷ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
⁸ Department of Medical Physiology, Faculty of Medicine, Mansoura University, Dakahlia, Egypt.
⁹ Department of Neurology, Faculty of Medicine, Mansoura University, Dakahlia, Egypt.
¹⁰ Department of Neurology, Mansoura International Hospital, Dakahlia, Egypt.
¹¹ Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Dakahlia, Egypt.
¹² Department of Neuropsychiatry, Faculty of Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt.
¹³ Department of Neurology, Faculty of Medicine, Alexandria University, Alexandia, Egypt.
¹⁴ Department of Internal Medicine, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Cairo, Egypt.
¹⁵ Faculty of Medicine, Newgiza University (NGU), Giza, Egypt.
¹⁶ Institute of Global Health and Human Ecology, The American University in Cairo, Cairo, Egypt. [email protected].
¹⁷ Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Dakahlia, Egypt. [email protected].
¹⁸ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK. [email protected].

PMID: 39505921
DOI: 10.1038/s41531-024-00826-8

Abstract

The impact of LRRK2 variants on the risk of Parkinson's disease in Egyptians remains unknown. We examined 1210 Egyptians (611 PD patients and 599 controls) from 16 governorates across Egypt for 12 LRRK2 pathogenic variants. The p.Gly2019Ser was the only variant detected, 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. Young and Early-onset PD prevalence was 37.5% in carriers and 33% in non-carriers. Familial cases were 16.6% in carriers and 11.5% in non-carriers. This study affirms that like other Mediterranean populations, Egyptians with PD have a higher prevalence of the p.Gly2019Ser variant compared to the global average. LRRK2 inhibitors could be promising therapeutic options for further exploration in this population.

Abstract

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