DPP6 gene disruption in a family with Gilles de la Tourette syndrome

Paolo Prontera, Valerio Napolioni, Valentina Ottaviani, Daniela Rogaia, Carmela Fusco, Bartolomeo Augello, Domenico Serino, Valentina Parisi, Laura Bernardini, Giuseppe Merla, Andrea E Cavanna, Emilio Donti

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Gilles de la Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and vocal tics, frequently associated with psychiatric co-morbidities. Despite the significant level of heritability, the genetic architecture of TS still remains elusive. Herein, we investigated an Italian family where an 8-year-old boy, his father, and paternal uncle have a diagnosis of TS. Array-CGH and high resolution SNP-array analyses revealed a heterozygous microdeletion of ∼135 kb at the 7q36.2 locus in the proband and his father. Fluorescent in situ hybridization and quantitative PCR (qPCR) analyses confirmed the presence of the alteration also in the paternal uncle. The deletion selectively involves the first exon of the DPP6 gene, leading to a down-regulation of its expression, as demonstrated by the reduced messenger RNA (mRNA) levels assessed by RT-qPCR. The DPP6 gene encodes for a type II membrane glycoprotein expressed predominantly in the central nervous system. To date, a de novo DPP6 exonic duplication, of uncertain significance, was reported in one patient with TS. Moreover, the DPP6 gene has been implicated in the pathogenesis of autism spectrum disorder (ASD) and, notably, in haloperidol-induced dyskinesia. This first familial case provides evidence for association between DPP6 haploinsufficiency and TS, further suggesting a plausible molecular link between TS and ASD, and might shed some light on the efficacy and tolerability profiles of antidopaminergic agents used for tic management, thus prompting further studies on a larger cohort of patients.

Original languageEnglish
Pages (from-to)237-242
Number of pages6
JournalNeurogenetics
Volume15
Issue number4
Early online date17 Aug 2014
DOIs
Publication statusPublished - Oct 2014

Keywords

  • Adult
  • Aged
  • Child
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics
  • Exons
  • Family
  • Family Health
  • Gene Deletion
  • Haploinsufficiency
  • Humans
  • Male
  • Nerve Tissue Proteins/genetics
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Potassium Channels/genetics
  • RNA, Messenger/metabolism
  • Tourette Syndrome/genetics
  • DPP6 gene
  • 7q microdeletion
  • Haloperidol
  • Autism
  • Attention-deficit and hyperactivity disorder

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