Identification of SYNJ1 in a Complex Case of Juvenile Parkinsonism Using a Multiomics Approach
This study aimed to elucidate the genetic causes underlying the juvenile parkinsonism (JP) diagnosed in a girl with several family members diagnosed with spinocerebellar ataxia type 2 (SCA2). To achieve this, whole-exome sequencing, analysis of CAG repeats, RNA sequencing analysis on fibroblasts, and metabolite identification were performed. As a result, a homozygous missense mutation SNP T>C (rs2254562) in synaptojamin 1 (SYNJ1), which has been implicated in the regulation of membrane trafficking in the synaptic vesicles, was identified. Additionally, we observed overexpression of L1 cell adhesion molecule (L1CAM), Cdc37, GPX1, and GPX4 and lower expression of ceruloplasmin in the patient compared to the control. We also found changes in sphingolipid, inositol, and inositol phosphate metabolism. These findings help to clarify the mechanisms of JP and suggest that the etiology of JP in the patient may be multifactorial. This is the first report of the rs2254562 mutation in the SYNJ gene identified in a JP patient with seizures and cognitive impairment.
Authors
- Victor García-Cabrera (ORCID: https://orcid.org/0000-0001-9320-0623)
- Luisa Arrabal (ORCID: https://orcid.org/0000-0001-6436-7029)
- Carmen Entrala‐Bernal
- Purificacion Gutierrez-Ríos
- José A. Lorente (ORCID: https://orcid.org/0000-0002-9892-7386)
- S. Roldán
- Jorge Sáiz (ORCID: https://orcid.org/0000-0003-1570-154X)
- Ester Leno‐Durán
- Francisco Fernández-Rosado
- Luis Javier Martínez-González (ORCID: https://orcid.org/0000-0003-2202-0662)
- Coral Barbas (ORCID: https://orcid.org/0000-0003-4722-491X)
- María‐José Sánchez (ORCID: https://orcid.org/0000-0003-4817-0757)
- Clara Alcántara-Domínguez
- Inmaculada Medina
Institutions
- Universidad San Pablo CEU (ES)
- Andalusian Health Service (ES)
- Universidad de Granada (ES)
- Instituto de Investigación Biosanitaria de Granada (ES)
- Hospital Universitario Virgen de las Nieves (ES)
- Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (ES)
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES)
- Andalusian School of Public Health (ES)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2024-09-09
- DOI
- https://doi.org/10.3390/ijms25179754
- Citations
- 1
- Primary Topic
- Cellular transport and secretion
- Type
- article
- Field-Weighted Citation Impact
- 0.33