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Background <p>The <i>GBA1</i> gene has been established as a notable risk factor in Parkinson's disease (PD). While some population-specific variants were reported, many regions of the world remain underexplored. This study investigates the prevalence, types, and clinical associations of <i>GBA1</i> variants in a large cohort of patients with PD (PwP) from Turkey.</p> Methods <p>A total of 716 individuals, including 513 PwP and 203 healthy controls (HC), were evaluated. Genetic analysis of <i>GBA1</i> variants was performed using nextgeneration sequencing. Additionally, whole exome sequencing (WES) was conducted on participants with detected <i>GBA1</i> variants. Clinical data, including motor, non-motor, and quality of life assessments, were collected. Enzyme and substrate levels were measured from dry blood spot samples.</p> Results <p><i>GBA1</i> variants were found in 13.2% of PD patients, significantly higher than in HC (6.4%), corresponding to an average 2.2-fold higher prevalence. The most frequent variants were p.T369M, p.L444P, and p.N370S. Additionally, 15 variants not previously reported in PD were detected. Patients with pathogenic variants had an earlier age of onset including a higher levodopa-equivalent daily dose and motor complications.</p> <p>Enzyme and substrate levels did not differ significantly between the groups. In one patient, WES data showed a <i>CTSB</i> variant which was reported to modify the effects of <i>GBA1</i>.</p> Conclusion <p>This is the largest study revealing prevalence of <i>GBA1</i> variants among PwP in Turkey, with significant clinical implications. The findings enrich the literature by expanding the previously unknown landscape of <i>GBA1</i> variants in this region.</p>

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Exploring GBA1 gene in Parkinson's disease: Prevalence and variant spectrum from Asia minor

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月20日

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  • Merve Koç Yekedüz,
  • Rezzak Yilmaz,
  • Talha Abali,
  • Sema Nur Kibrit,
  • Ahmet Veli Karacan,
  • Elif Yüsra Unutmaz,
  • Gülnur Ayık,
  • Dudu Genç-Batmaz,
  • G. Rana Dilek,
  • Binnur Çelik,
  • Emine Gemci,
  • Turgut Şahin,
  • Ahmet Yalcin,
  • Serdar Ceylaner,
  • M. Cenk Akbostancı,
  • Fatma Tuba Eminoğlu

摘要

Background

The GBA1 gene has been established as a notable risk factor in Parkinson's disease (PD). While some population-specific variants were reported, many regions of the world remain underexplored. This study investigates the prevalence, types, and clinical associations of GBA1 variants in a large cohort of patients with PD (PwP) from Turkey.

Methods

A total of 716 individuals, including 513 PwP and 203 healthy controls (HC), were evaluated. Genetic analysis of GBA1 variants was performed using nextgeneration sequencing. Additionally, whole exome sequencing (WES) was conducted on participants with detected GBA1 variants. Clinical data, including motor, non-motor, and quality of life assessments, were collected. Enzyme and substrate levels were measured from dry blood spot samples.

Results

GBA1 variants were found in 13.2% of PD patients, significantly higher than in HC (6.4%), corresponding to an average 2.2-fold higher prevalence. The most frequent variants were p.T369M, p.L444P, and p.N370S. Additionally, 15 variants not previously reported in PD were detected. Patients with pathogenic variants had an earlier age of onset including a higher levodopa-equivalent daily dose and motor complications.

Enzyme and substrate levels did not differ significantly between the groups. In one patient, WES data showed a CTSB variant which was reported to modify the effects of GBA1.

Conclusion

This is the largest study revealing prevalence of GBA1 variants among PwP in Turkey, with significant clinical implications. The findings enrich the literature by expanding the previously unknown landscape of GBA1 variants in this region.