Identification of rare variants in KCTD13 at the schizophrenia risk locus 16p11.2.
Duplications in 16p11.2 are a risk factor for schizophrenia (SCZ). Using genetically modified zebrafish, Golzio and colleagues identified KCTD13 within 16p11.2 as a major driver of the neuropsychiatric phenotype observed in humans. The aims of the present study were to explore the role of KCTD13 in the development of SCZ and to provide a more complete picture of the allelic architecture at this risk locus. The exons of KCTD13 were sequenced in 576 patients. The mutations c.6G>T and c.598G>A were identified in one patient each. Both mutations were predicted to be functionally relevant and were absent from the 1000 Genomes Project data and the Exome Variant Server. The mutation c.6G>T was predicted to abolish a potential transcription factor-binding site for specifity protein 1. Altered specifity protein 1 expression has been reported in SCZ patients compared with controls. Further studies in large cohorts are warranted to determine the relevance of the two identified mutations.
aInstitute of Human Genetics bDepartment of Genomics, Life and Brain Center cDepartment of Psychiatry and Psychotherapy dDepartment of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn eDepartment of Psychiatry, Ludwig-Maximilians-University Munich fKbo Kliniken des Bezirks Oberbayern, Munich gDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg hDepartment of Psychiatry, University of Halle-Wittenberg, Halle iIsar Amper Klinikum München Ost, kbo, Haar jInstitute of Neuroscience and Medicine (INM-1), Structural and Functional Organisation of the Brain, Genomic Imaging, Research Centre Juelich, Juelich, Germany kFaculty of Science, Medicine & Health, University of Wollongong, Wollongong, Australia lDepartment of Biomedicine, Division of Medical Genetics, University Hospital Basel, University of Basel, Basel, Switzerland.
Franziska
F
Degenhardt
Barbara
B
Heinemann
Jana
J
Strohmaier
Marvin A
MA
Pfohl
Ina
I
Giegling
Andrea
A
Hofmann
Kerstin U
KU
Ludwig
Stephanie H
SH
Witt
Michael
M
Ludwig
Andreas J
AJ
Forstner
Margot
M
Albus
Sibylle G
SG
Schwab
Margitta
M
Borrmann-Hassenbach
Leonard
L
Lennertz
Michael
M
Wagner
Per
P
Hoffmann
Dan
D
Rujescu
Wolfgang
W
Maier
Sven
S
Cichon
Marcella
M
Rietschel
Markus M
MM
Nöthen
D000328:Adult; D000483:Alleles; D002885:Chromosomes, Human, Pair 16; D056915:DNA Copy Number Variations; D059472:Exome; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics*
C439978:KCTD13 protein, human; D009687:Nuclear Proteins
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