title: A W148R mutation in the human FOXD4 gene segregating with dilated cardiomyopathy, obsessive-compulsive disorder, and suicidality.
abstract: 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.
authors.affiliation: Interdepartmental Center for Research in Molecular Medicine (CIRMC), University of Pavia, I-27100, Pavia, Italy.
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Minoretti
authors.forename: Mariarosa
authors.initials: M
authors.lastname: Arra
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuele
authors.forename: Valentina
authors.initials: V
authors.lastname: Olivieri
authors.forename: Alessia
authors.initials: A
authors.lastname: Aldeghi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Politi
authors.forename: Valentina
authors.initials: V
authors.lastname: Martinelli
authors.forename: Sara
authors.initials: S
authors.lastname: Pesenti
authors.forename: Colomba
authors.initials: C
authors.lastname: Falcone
mesh_terms: 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*
chemical_list: C470165:FOXD4 protein, human; D051858:Forkhead Transcription Factors; D014364:Tryptophan; D001120:Arginine