title: Two novel mutations of the IRX4 gene in patients with congenital heart disease.
abstract: IRX4 was the first identified cardiac transcription factor that is restricted to the ventricles at all stages of heart development. Irx4-deficient mice show ventricular dysfunction and develop cardiomyopathy. To study the potential impact of sequence variations in IRX4 on congenital heart disease (CHD) in humans, we examined the coding region of IRX4 in a cohort of 698 Chinese people with congenital heart disease and 250 healthy individuals as the controls. We found two potential disease-causing mutations, p. Asn85Tyr and p. Glu92Gly. A mammalian two-hybrid assay showed that both of the mutations significantly affected the interaction between IRX4 and RXRA. It demonstrated that IRX4 had a potential causative impact on the development of congenital heart disease, particularly ventricular septal defect.
authors.affiliation: Graduate School, Peking Union Medical College, Beijing, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Cheng
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Su
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.forename: Guoying
authors.initials: G
authors.lastname: Huang
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Li
authors.forename: Zhongzhi
authors.initials: Z
authors.lastname: Li
authors.forename: Adong
authors.initials: A
authors.lastname: Shen
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xie
authors.forename: Binbin
authors.initials: B
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D015331:Cohort Studies; D006330:Heart Defects, Congenital / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D047488:Retinoid X Receptors / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C485533:IRX4 protein, human; D047488:Retinoid X Receptors