De novo SCN1A missense variant in a patient with Parkinson's disease

Majed Alluqmani; Abdulfatah M Alayoubi; Jamil A Hashmi; Sulman Basit

doi:10.3389/fgene.2024.1496683

De novo SCN1A missense variant in a patient with Parkinson's disease

Front Genet. 2024 Nov 6:15:1496683. doi: 10.3389/fgene.2024.1496683. eCollection 2024.

Authors

Majed Alluqmani¹, Abdulfatah M Alayoubi², Jamil A Hashmi^{2

3}, Sulman Basit^{2

3}

Affiliations

¹ Department of Neurology, College of Medicine, Taibah University Medina, Medina, Saudi Arabia.
² Department of Basic Medical Sciences, College of Medicine, Taibah University Medina, Medina, Saudi Arabia.
³ Center for Genetics and Inherited Diseases, Taibah University Medina, Medina, Saudi Arabia.

Abstract

Background: Variants in a gene encoding sodium voltage-gated channel alpha subunit 1 (SCN1A) are known to cause a broad clinical spectrum of epilepsy and associated features, including Dravet syndrome (MIM 607208), non-Dravet developmental and epileptic encephalopathy (MIM 619317), familial febrile seizures (MIM 604403), familial hemiplegic migraine (MIM 609634), and generalized epilepsy with febrile seizures (MIM 604403).

Methods: In this study, we examined a patient with Parkinson's disease (PD) without any clinical manifestations of epilepsy and associated features. Genomic nucleic acid was extracted, and a complete coding sequence of the human genome (whole-exome sequencing) was sequenced. Moreover, Sanger sequencing of variants of interest was performed to validate the exome-discovered variants.

Results: We identified a heterozygous pathogenic missense mutation (c.1498C>T; p.Arg500Trp) in the SCN1A gene in the patient using the whole-exome sequencing approach. The onset of PD features in our patient occurred at the age of 30 years. Biochemical investigations were carried out to rule out any secondary cause of the disease, including Wilson's disease or another metabolic disorder. MRI of the brain and spinal images were unremarkable. Moreover, a dramatic response to carbidopa-levodopa treatment was also observed in the patient.

Conclusion: Our results suggest that the pathogenic variant in SCN1A may lead to PD features without epilepsy.

Keywords: Parkinson’s disease; SCN1A gene; exome sequencing; mutation; no epilepsy.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The authors extend their appreciation to the King Salman Center for Disability Research, Riyadh, Saudi Arabia, for funding this work through Research Group no. KSRG-2022-088. The funding body played no role in the design of the study and collection, analysis, and interpretation of the data and in writing the manuscript.