L-histidine decarboxylase and Tourette's syndrome

  • N Engl J Med. 2010 May 20;362(20):1901-8. doi: 10.1056/NEJMoa0907006.
A Gulhan Ercan-Sencicek  1 ,  Althea A Stillman ,  Ananda K Ghosh ,  Kaya Bilguvar ,  Brian J O'Roak ,  Christopher E Mason ,  Thomas Abbott ,  Abha Gupta ,  Robert A King ,  David L Pauls ,  Jay A Tischfield ,  Gary A Heiman ,  Harvey S Singer ,  Donald L Gilbert ,  Pieter J Hoekstra ,  Thomas M Morgan ,  Erin Loring ,  Katsuhito Yasuno ,  Thomas Fernandez ,  Stephan Sanders ,  Angeliki Louvi ,  Judy H Cho ,  Shrikant Mane ,  Christopher M Colangelo ,  Thomas Biederer ,  Richard P Lifton ,  Murat Gunel ,  Matthew W State
Affiliations
  • 1. Yale University School of Medicine, New Haven, CT 06520, USA.
PMID: 20445167 DOI: 10.1056/NEJMoa0907006
Abstract

Tourette's syndrome is a common developmental neuropsychiatric disorder characterized by chronic motor and vocal tics. Despite a strong genetic contribution, inheritance is complex, and risk alleles have proven difficult to identify. Here, we describe an analysis of linkage in a two-generation pedigree leading to the identification of a rare functional mutation in the HDC gene encoding L-histidine decarboxylase, the rate-limiting enzyme in histamine biosynthesis. Our findings, together with previously published data from model systems, point to a role for histaminergic neurotransmission in the mechanism and modulation of Tourette's syndrome and tics.