The Role of Gene Expression Dysregulation in the Pathogenesis of Mucopolysaccharidosis: A Comparative Analysis of Shared and Specific Molecular Markers in Neuronopathic and Non-Neuronopathic Types of the Disease.

Mucopolysaccharidosis (MPS) comprises a group of inherited metabolic diseases. Each MPS type is caused by a deficiency in the activity of one kind of enzymes involved in glycosaminoglycan (GAG) degradation, resulting from the presence of pathogenic variant(s) of the corresponding gene. All types/subtypes of MPS, which are classified on the basis of all kinds of defective enzymes and accumulated GAG(s), are severe diseases. However, neuronopathy only occurs in some MPS types/subtypes (specifically severe forms of MPS I and MPS II, all subtypes of MPS III, and MPS VII), while in others, the symptoms related to central nervous system dysfunctions are either mild or absent. The early diagnosis of neuronopathy is important for the proper treatment and/or management of the disease; however, there are no specific markers that could be easily used for this in a clinical practice. Therefore, in this work, a comparative analysis of shared and specific gene expression alterations in neuronopathic and non-neuronopathic MPS types was performed using cultures of cells derived from patients. Using transcriptomic analyses (based on the RNA-seq method, confirmed by measuring the levels of a selected gene product), we identified genes (including