COMT Val(158)Met Polymorphism Is Associated with Verbal Working Memory in Neurofibromatosis Type 1.

Danielle De Souza Costa,Patrícia A Pereira,Débora M De Miranda,Leandro F Malloy-Diniz,Marco A Romano-Silva,Jonas J De Paula,Luiz O C Rodrigues,Antonio M Alvim-Soares

doi:10.3389/fnhum.2016.00334

Abstract

Neurofibromatosis type I (NF1) is a neurogenetic disease marked by multiple cognitive and learning problems. Genetic variants may account for phenotypic variance in NF1. Here, we investigated the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and working memory and arithmetic performance in 50 NF1 individuals. A significant association of the COMT polymorphism was observed only with verbal working memory, as measured by the backward digit-span task with an advantageous performance for Met/Met carriers. To study how genetic modifiers influence NF1 cognitive performance might be of importance to decrease the unpredictability of the cognitive profile among NF1 patients.

Highlights

Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder affecting 1 in each 3500 individuals (Friedman, 1999; Ferner, 2007)
Our preliminary results support an advantageous working memory performance in NF1 Met/Met carriers, which strengthens the hypothesis of genetic variants accounting for phenotypic variability in NF1
COMT polymorphism effect on working memory (Mier et al, 2010; Bellander et al, 2015), we add into this line of evidence showing a COMT Val158Met genotype effect on cognitive control even in a sample of subjects with a monogenic disorder with compromising of behavior and cognition

Summary

Introduction

Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder affecting 1 in each 3500 individuals (Friedman, 1999; Ferner, 2007). NF1 is caused by mutations only in the NF1 gene and have an autosomal dominant inheritance (Easton et al, 1993; Ward and Gutmann, 2005; Sabbagh et al, 2009). This single-gene disease is marked by cognitive, learning, and behavioral problems and is a potential model for the investigation of the biological mechanisms related to these complex phenotypes (Shilyansky et al, 2010). Cognitive impairment and academic failure are the most common reported problems in the clinical care of NF1 individuals (Hyman et al, 2005). NF1 phenotype varies from minimal to maximal presentation in all clinical characteristics, and cognitive and behavioral aspects are not an exception (Shilyansky et al, 2010)

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