title: Executive functions are impaired in heterozygote patients with oculopharyngeal muscular dystrophy.
abstract: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disorder caused by a small expansion of a short polyalanine tract in poly(A) binding protein nuclear 1 (PABPN1). It presents with adult onset of progressive eyelid drooping, swallowing difficulties and proximal limb weakness, usually without involvement of central nervous system (CNS). However, cognitive decline with relevant behavioural and psychological symptoms has been recently described in homozygous patients. In this study, we performed for the first time an extensive neuropsychological and neuropsychiatric evaluation on 11 OPMD heterozygote patients. We found that they were less efficient than a matched control sample on several tests, particularly those tapping executive functions. Moreover, the presence of negative correlation between GCN expansion size and some neuropsychological scores raises the issue that CNS involvement might be linked to the genetic defect, being worse in patients with larger expansion. Our results might be consistent with the toxic gain-of-function theory in the pathogenesis of OPMD and hint at a possible direct role of PABPN1 in the CNS also in heterozygote patients.
authors.affiliation: Department of Neurological Sciences, University Federico II of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Dubbioso
authors.forename: Pasquale
authors.initials: P
authors.lastname: Moretta
authors.forename: Fiore
authors.initials: F
authors.lastname: Manganelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Fiorillo
authors.forename: Rosa
authors.initials: R
authors.lastname: Iodice
authors.forename: Luigi
authors.initials: L
authors.lastname: Trojano
authors.forename: Lucio
authors.initials: L
authors.lastname: Santoro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000209:etiology*; D004576:Electromyography; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D039141:Muscular Dystrophy, Oculopharyngeal / Q000150:complications* / Q000235:genetics*; D009483:Neuropsychological Tests; D039103:Poly(A)-Binding Protein II / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: D039103:Poly(A)-Binding Protein II