title: Novel point mutation in the cardiac transcription factor CSX/NKX2.5 associated with congenital heart disease.
abstract: The homeobox transcription factor CSX/NKX2.5, which is a vertebrate homologue of the Drosophila gene tinman, is essential for cardiac development. It is expressed in the early cardiac mesoderm and in heart muscle lineage throughout life. Homozygous deletion of CSX/NKX2.5 causes early embryonic lethality in mice because cardiac development is arrested at the linear heart tube stage. Heterozygous mutation of human CSX/NKX2.5 has been associated with various congenital heart diseases such as atrial septal defect (ASD), ventricular septal defect, tetralogy of Fallot, and tricuspid valve abnormalities, including Ebstein's anomaly. Additionally, CSX/NKX2.5 mutation causes atrioventricular (AV) conduction block with or without associated congenital heart diseases. Ten different heterozygous mutations have been already reported and a new point mutation, which is a C-to-A transition (Cys264ter) at nucleotide 901 of CSX/NKX2.5, results in the production of a truncated protein occurring COOH-terminal to the homeodomain of CSX/NKX2.5. The mutation was found in a patient with familial ASD and first-degree AV block; 4 members from 3 generations had secundum-type ASD and first-degree AV block.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hiroi
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoda
authors.forename: Toshinori
authors.initials: T
authors.lastname: Utsunomiya
authors.forename: Shuzo
authors.initials: S
authors.lastname: Matsuo
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ito
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Inoue
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sumiyoshi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takano
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D003545:Cysteine; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D014157:Transcription Factors / Q000235:genetics*; D029867:Xenopus Proteins
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors; D029867:Xenopus Proteins; D003545:Cysteine