Category: Parkinson's Disease: Genetics
Objective: To identify novel genes involved in the familial form of Parkinson’s disease (PD) in the Indian population.
Background: Most of the familial forms of genes implicated in PD have been identified in the European population with limited transferability in ethnically diverse populations such as the Indian population.
Method: Exome sequencing in a large PD family from India with multiple affected (4 affected and 2 unaffected) was performed. The targeted resequencing was performed in an independent cohort of 714 PD cases and 362 controls from the Indian population. Furthermore, whole-exome sequencing (WES) data from the IPDGC, which includes 1,167 PD cases and 1,685 controls (post-QC) and additional 200 exomes from Vienna were screened to assess and identify the frequency of the novel variants in the European population.
Results: We found a missense mutation, c.1151A>T/ p.Tyr384Phe (exon 8) in the SLC1A7 gene, encoding Excitatory Amino Acid Transporter 5 (EAAT5), in all four affected family members. Targeted resequencing identified four additional nonsynonymous missense variants (based on CADD filtering and missense variant), including c.1151A>T/ p.Tyr384Phe, in a sporadic PD case and in a single control in the Indian population. SLC1A7 gene mutation predictions showed the mutation has a destabilizing role. The observed mutation is likely to disrupt the hydrogen bond network and probably affects how the SLC1A7 gene binds to glutamate/aspartate substrates. WES data from the IPDGC identified one PD case carrying a missense variant, c,835A>T:p, T279S (exon 10) and absent in 1685 exome controls. Likewise, the Vienna cohort revealed the missense variant (c.259G->A: Arg87Cys) within the SLC1A7 gene segregating in a family consisting of mother and son (both affected) indicating the role of the SLC1A7 mutations in PD pathogenesis.
Conclusion: Our findings implicate the role of the rare mutations in the SLC1A7 gene in the pathogenesis of PD.
To cite this abstract in AMA style:
A. Kishore, M. Marc Sturm, F. Raimondi, P. Lichtner, A. Sreelatha, N. Casadei, C. Blauwendraat, G. Sarma, R. Kruger, A. Zimprich, A. Singleton, T. Gasser, O. Riess, M. Sharma. SLC1A7 mutation is a cause of the autosomal dominant form of Parkinson’s disease [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/slc1a7-mutation-is-a-cause-of-the-autosomal-dominant-form-of-parkinsons-disease/. Accessed June 14, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/slc1a7-mutation-is-a-cause-of-the-autosomal-dominant-form-of-parkinsons-disease/