L-histidine decarboxylase and Tourette's syndrome.
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.
Ercan-Sencicek
A Gulhan
AG
Yale University School of Medicine, New Haven, CT 06520, USA.
Stillman
Althea A
AA
Ghosh
Ananda K
AK
Bilguvar
Kaya
K
O'Roak
Brian J
BJ
Mason
Christopher E
CE
Abbott
Thomas
T
Gupta
Abha
A
King
Robert A
RA
Pauls
David L
DL
Tischfield
Jay A
JA
Heiman
Gary A
GA
Singer
Harvey S
HS
Gilbert
Donald L
DL
Hoekstra
Pieter J
PJ
Morgan
Thomas M
TM
Loring
Erin
E
Yasuno
Katsuhito
K
Fernandez
Thomas
T
Sanders
Stephan
S
Louvi
Angeliki
A
Cho
Judy H
JH
Mane
Shrikant
S
Colangelo
Christopher M
CM
Biederer
Thomas
T
Lifton
Richard P
RP
Gunel
Murat
M
State
Matthew W
MW
D002874:Chromosome Mapping; D018389:Codon, Nonsense; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006640:Histidine Decarboxylase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D016133:Polymerase Chain Reaction; D005879:Tourette Syndrome / Q000235:genetics*
D018389:Codon, Nonsense; D006640:Histidine Decarboxylase
Physiol Rev. 2008 Jul;88(3):1183-241
18626069
Arch Gen Psychiatry. 1985 Aug;42(8):815-20
3860194
Inflamm Res. 2005 Apr;54 Suppl 1:S23-4
15928819
Neuropsychopharmacology. 2002 Jul;27(1):92-104
12062910
J Child Neurol. 2006 Aug;21(8):642-9
16970864
J Pharmacol Exp Ther. 2005 Apr;313(1):176-90
15608077
Eur J Neurosci. 2004 Aug;20(4):1051-8
15305873
J Neurochem. 2002 Nov;83(4):837-45
12421355
Science. 2005 Oct 14;310(5746):317-20
16224024
Brain Dev. 2003 Dec;25 Suppl 1:S15-9
14980366
J Biol Chem. 2003 Jan 3;278(1):686-94
12414789
Biochem Pharmacol. 2007 Apr 15;73(8):1215-24
17343831
J Biol Chem. 1992 Nov 15;267(32):23057-62
1429654
FEBS Lett. 2001 Jul 27;502(1-2):53-6
11478947
Cell. 2001 Feb 23;104(4):545-56
11239411
Behav Brain Res. 2006 Mar 15;168(1):92-9
16310870
Mol Psychiatry. 2010 Feb;15(2):177-84
18794888
Biochem Biophys Res Commun. 2003 Jun 6;305(3):443-7
12763012
Am J Hum Genet. 2007 Sep;81(3):559-75
17701901
Nat Genet. 2004 Sep;36(9):949-51
15286789