Phenotype Correlations of Neurological Manifestations in Wolfram Syndrome: Predictive Modeling in a Spanish Cohort.

ABSTRACT: Background: Wolfram syndrome (WS) is an ultrarare neuroendocrine disorder caused by pathogenic variants in WFS1, frequently leading to progressive neurological, autonomic, and cognitive impairment. Anticipating neurological trajectories remains challenging due to marked phenotypic variability and limited genotype-phenotype data. Methods: Forty-five genetically confirmed patients with WS were evaluated between 1998 and 2024 in Spain. All WFS1 variants were systematically classified by exon, zygosity, protein-level functional impact, and predicted wolframin production (Classes 0-3). Machine learning models (Random Forests with engineered gene-gene interaction terms) were applied to predict neurological manifestations and identify the strongest genetic determinants of symptom se

SUBMITTER: Esteban-Bueno G 

PROVIDER: S-EPMC12732145 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature