Identification of SYNJ1 in a Complex Case of Juvenile Parkinsonism Using a Multiomics Approach

• Published in: International journal of molecular sciences Vol. 25; no. 17; p. 9754
• Main Authors: Leno-Durán, Ester, Arrabal, Luisa, Roldán, Susana, Medina, Inmaculada, Alcántara-Domínguez, Clara, García-Cabrera, Victor, Saiz, Jorge, Barbas, Coral, Sánchez, Maria José, Entrala-Bernal, Carmen, Fernández-Rosado, Francisco, Lorente, Jose Antonio, Gutierrez-Ríos, Purificacion, Martínez-Gonzalez, Luis Javier
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.09.2024
• Subjects: Age; Amino acids; Ataxia; Child; Child development; Convulsions & seizures; Diagnosis; Disease; Dystonia; Epilepsy; Exome Sequencing; Families & family life; Family medical history; Female; Genes; Genetic aspects; Genotype & phenotype; Health aspects; Humans; Identification and classification; Juvenile Parkinsonism; metabolism; Movement disorders; Multiomics; Mutation; mutation screening; Mutation, Missense; Nerve Tissue Proteins - genetics; Neurodegeneration; Parkinsonian Disorders - genetics; Parkinsonism; Pathogenesis; Patients; Pediatric research; Pedigree; Phosphatase; Polymorphism, Single Nucleotide; Single nucleotide polymorphisms; SYNJ1; Tremor (Muscular contraction); whole-exome sequencing; Spain; Iran; mutation screening; Juvenile Parkinsonism; metabolism; multiomics; SYNJ1; whole-exome sequencing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25179754

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.