Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family.
Holt-Oram syndrome is a developmental disorder affecting the heart and upper limb, the gene for which was mapped to chromosome 12 two years ago. We have now identified a gene for this disorder (HOS1). The gene (TBX5) is a member of the Brachyury (T) family corresponding to the mouse Tbx5 gene. We have identified six mutations, three in HOS families and three in sporadic HOS cases. Each of the mutations introduces a premature stop codon in the TBX5 gene product. Tissue in situ hybridization studies on human embryos from days 26 to 52 of gestation reveal expression of TBX5 in heart and limb, consistent with a role in human embryonic development.
Li
Q Y
QY
Department of Genetics, University of Nottingham, Queen's Medical Centre, UK.
Newbury-Ecob
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Terrett
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JA
Wilson
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Curtis
A R
AR
Yi
C H
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Gebuhr
T
T
Bullen
P J
PJ
Robson
S C
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Strachan
T
T
Bonnet
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Lyonnet
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Young
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Raeburn
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Buckler
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Law
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Brook
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D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001132:Arm / Q000002:abnormalities*; D001483:Base Sequence; D002460:Cell Line; D018244:Chromosomes, Artificial, Yeast; D002881:Chromosomes, Human, Pair 12; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005326:Fetal Proteins / Q000235:genetics; D015870:Gene Expression; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D000098908:Brachyury Protein
D004247:DNA; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein; C103172:T-box transcription factor 5