A W148R mutation in the human FOXD4 gene segregating with dilated cardiomyopathy, obsessive-compulsive disorder, and suicidality.
The forkhead/winged helix box (FOX) gene family comprises at least 43 different genes encoding transcriptional factors with a highly conserved DNA-binding domain. To date, mutations in members of the FOX gene family have been causally linked to a variety of different human diseases. We describe a three-generation Albanian pedigree in which a complex phenotype consisting of dilated cardiomyopathy, obsessive-compulsive disorder, and suicidality is segregated with a missense mutation (W148R) in the human FOXD4 gene. This mutation disrupts an extremely highly conserved tryptophan residue in the forkhead domain of FOXD4, possibly resulting in reduced DNA binding capacity and altered transcriptional activity. Our present findings widen the spectrum of diseases associated with genetic aberrations in the forkhead gene family.
Minoretti
Piercarlo
P
Interdepartmental Center for Research in Molecular Medicine (CIRMC), University of Pavia, I-27100, Pavia, Italy.
Arra
Mariarosa
M
Emanuele
Enzo
E
Olivieri
Valentina
V
Aldeghi
Alessia
A
Politi
Pierluigi
P
Martinelli
Valentina
V
Pesenti
Sara
S
Falcone
Colomba
C
D000328:Adult; D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics*; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000150:complications* / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009771:Obsessive-Compulsive Disorder / Q000150:complications* / Q000235:genetics; D010375:Pedigree; D013405:Suicide; D014364:Tryptophan / Q000235:genetics*
C470165:FOXD4 protein, human; D051858:Forkhead Transcription Factors; D014364:Tryptophan; D001120:Arginine