RT Journal Article
T1 Identification of SYNJ1 in a Complex Case of Juvenile Parkinsonism Using a Multiomics Approach.
A1 Leno-Durán, Ester
A1 Arrabal, Luisa
A1 Roldán, Susana
A1 Medina-Cáliz, Inmaculada
A1 Alcántara-Domínguez, Clara
A1 García-Cabrera, Victor
A1 Saiz, Jorge
A1 Barbas, Coral
A1 Sanchez-Perez, Maria-Jose
A1 Entrala-Bernal, Carmen
A1 Fernández-Rosado, Francisco
A1 Lorente, Jose Antonio
A1 Gutierrez-Ríos, Purificacion
A1 Martínez-Gonzalez, Luis Javier
K1 Juvenile Parkinsonism
K1 SYNJ1
K1 Metabolism
K1 Multiomics
K1 Mutation screening
K1 Whole-exome sequencing
AB 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.
PB MDPI
YR 2024
FD 2024-09-09
LK https://hdl.handle.net/10668/24312
UL https://hdl.handle.net/10668/24312
LA en
NO Leno-Durán E, Arrabal L, Roldán S, Medina I, Alcántara-Domínguez C, García-Cabrera V, et al. Identification of SYNJ1 in a Complex Case of Juvenile Parkinsonism Using a Multiomics Approach. Int J Mol Sci. 2024 Sep 9;25(17):9754.
NO This research was funded by Fundación Mutua Madrileña, Spain (XIII Call on Research Grants 2016), reference number AP163052016.
DS RISalud
RD Sep 6, 2025