Congenital heart disease caused by mutations in the transcription factor NKX2-5.
Mutations in the gene encoding the homeobox transcription factor NKX2-5 were found to cause nonsyndromic, human congenital heart disease. A dominant disease locus associated with cardiac malformations and atrioventricular conduction abnormalities was mapped to chromosome 5q35, where NKX2-5, a Drosophila tinman homolog, is located. Three different NKX2-5 mutations were identified. Two are predicted to impair binding of NKX2-5 to target DNA, resulting in haploinsufficiency, and a third potentially augments target-DNA binding. These data indicate that NKX2-5 is important for regulation of septation during cardiac morphogenesis and for maturation and maintenance of atrioventricular node function throughout life.
Schott
J J
JJ
Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Benson
D W
DW
Basson
C T
CT
Pease
W
W
Silberbach
G M
GM
Moak
J P
JP
Maron
B J
BJ
Seidman
C E
CE
Seidman
J G
JG
D000595:Amino Acid Sequence; D000818:Animals; D001283:Atrioventricular Node / Q000503:physiopathology; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D003062:Codon; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006327:Heart Block / Q000235:genetics* / Q000503:physiopathology; D006344:Heart Septal Defects, Atrial / Q000235:genetics* / Q000503:physiopathology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D014176:Protein Biosynthesis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D029867:Xenopus Proteins
D003062:Codon; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; D029867:Xenopus Proteins