Visual and cognitive functioning in patients with Duchenne Muscular Dystrophy with genetic mutations that alter the expression of the dystrophin Dp71 protein.

• Grant number: 21/05442-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2022
• End date: February 28, 2025
• Field of knowledge: Humanities - Psychology - Experimental Psychology
• Principal Investigator: Dora Selma Fix Ventura
• Grantee: Sarah Leonardo Dias
• Host Institution: Instituto de Psicologia (IP). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 14/26818-2 - Development and implementation of visual evaluation methods: clinical applications and animal models, AP.TEM

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease resulting from mutations or deletions in the DMD gene. It affects the expression of dystrophin proteins (Dps) leading to severe muscle impairment. The Dps are also required for the proper functioning of the central nervous system (CNS). The retina and the brain cells express at least four types of Dps. Previous studies showed that alterations of the DMD gene which affect the expression of the Dp260 cause functional alterations in the retina leading to visual symptoms which are identified by the reduction of the b-wave of the full field electroretinogram (ERG) and decrease of rod sensitivity. However, more distal genetic alterations in the DMD gene, which are rare and affect the expression of all Dps including the Dp71 were not systematically investigated. It is intriguing the fact that the rod sensitivity loss is associated with mutations of the Dp260, but not with mutations compromising the Dp71 (which include all Dps), as we recently observed in a pilot study, while in the brain, accumulated alterations of Dps results in more severe cognitive phenotypes. The aim of this study is to evaluate the visual functions (color vision, contrast sensitivity and dark adaptation) and the cognitive functions (Wechsler Intelligence Scale and Child and adolescent behavior inventory) of DMD patients and compare the results of subjects with genetic alterations upstream exon 63 (preserved Dp71) and downstream this exon (affected Dp71) with control subjects. We will evaluate 20 subjects in each group. If our preliminary findings are confirmed, a previously unsuspected relationship of Dp proteins interactions in the CNS could be identified. One hypothesis for this functional compensation could be that the accumulated alteration of dystrophin proteins would stimulate alternative compensatory mechanisms.