A novel missense mutation in the transmembrane domain of neuregulin 1 is associated with schizophrenia.
BACKGROUND
Although genetic factors are known to play an important role in schizophrenia, the identification of genes involved in this disorder has remained elusive. The neuregulin 1 gene is among the few candidate genes to have been implicated in schizophrenia susceptibility in several populations. However, no causal mutations within this gene have been identified.


METHODS
In attempts to identify polymorphisms within the neuregulin 1 gene, we performed DNA sequencing using 12 subjects with a history of psychosis from the Central Valley of Costa Rica. DNA genotyping and association studies were then performed in an extended cohort of 142 affected individuals and their relatives from the same population.


RESULTS
We identified a novel missense mutation (Val to Leu) in exon 11, which codes for the transmembrane region of the neuregulin 1 protein. Association analysis by the Family Based Association Test (FBAT) revealed that this mutation is associated with psychosis (p = .0049) and schizophrenia (p = .0191) in this population.


CONCLUSIONS
We report the finding of a missense mutation in the neuregulin 1 gene associated with schizophrenia. Additional analyses of an independent sample as well as detailed functional studies should be performed to determine the relevance of this novel polymorphism to the pathophysiology of schizophrenia.
Walss-Bass
Consuelo
C
Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas, USA.
Liu
Wei
W
Lew
Debbie F
DF
Villegas
Ramon
R
Montero
Patricia
P
Dassori
Albana
A
Leach
Robin J
RJ
Almasy
Laura
L
Escamilla
Michael
M
Raventos
Henriette
H
D000818:Animals; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007930:Leucine / Q000235:genetics; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D020890:Neuregulin-1 / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D017434:Protein Structure, Tertiary / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D017385:Sequence Homology; D014633:Valine / Q000235:genetics
D020890:Neuregulin-1; D007930:Leucine; D014633:Valine