| Autor: |
Leno-Durán E; Department of Obstetrics and Gynecology, Faculty of Medicine, University of Granada, 18016 Granada, Spain., Arrabal L; Pediatric Neurology Department, Hospital Virgen de las Nieves, 18014 Granada, Spain., Roldán S; Pediatric Neurology Department, Hospital Virgen de las Nieves, 18014 Granada, Spain., Medina I; Pediatric Neurology Department, Hospital Virgen de las Nieves, 18014 Granada, Spain., Alcántara-Domínguez C; Centre for Genomics and Oncological Research (GENYO), Pfizer, University of Granada, Andalusian Regional Government, PTS, 18016 Granada, Spain., García-Cabrera V; Centre for Genomics and Oncological Research (GENYO), Pfizer, University of Granada, Andalusian Regional Government, PTS, 18016 Granada, Spain., Saiz J; Centre for Metabolomics and Bionanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty, Universidad CEU San Pablo, 28926 Madrid, Spain., Barbas C; Centre for Metabolomics and Bionanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty, Universidad CEU San Pablo, 28926 Madrid, Spain., Sánchez MJ; CIBER Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain.; Andalusian School of Public Health (EASP), 18080 Granada, Spain.; Instituto de Investigación Biosanitaria, ibs. GRANADA, 18012 Granada, Spain., Entrala-Bernal C; Lorgen G.P., PT, Ciencias de la Salud-Business Innovation Centre (BIC), 18016 Granada, Spain., Fernández-Rosado F; Lorgen G.P., PT, Ciencias de la Salud-Business Innovation Centre (BIC), 18016 Granada, Spain., Lorente JA; Centre for Genomics and Oncological Research (GENYO), Pfizer, University of Granada, Andalusian Regional Government, PTS, 18016 Granada, Spain.; Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine-PTS, University of Granada, 18016 Granada, Spain., Gutierrez-Ríos P; Jaen-Sur Health District, Andalusian Health Service, Andalusian Regional Government, 23009 Jaén, Spain., Martínez-Gonzalez LJ; Centre for Genomics and Oncological Research (GENYO), Pfizer, University of Granada, Andalusian Regional Government, PTS, 18016 Granada, Spain.; Department of Biochemistry, Molecular Biology III and Immunology, Faculty of Medicine, University of Granada, 18016 Granada, Spain. |
| Abstrakt: |
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. |
