Mutation in myosin heavy chain 6 causes atrial septal defect

被引:0
作者
Yung-Hao Ching
Tushar K Ghosh
Steve J Cross
Elizabeth A Packham
Louise Honeyman
Siobhan Loughna
Thelma E Robinson
Andrew M Dearlove
Gloria Ribas
Andrew J Bonser
Neil R Thomas
Andrew J Scotter
Leo S D Caves
Graham P Tyrrell
Ruth A Newbury-Ecob
Arnold Munnich
Damien Bonnet
J David Brook
机构
[1] Institute of Genetics,Department of Biology
[2] University of Nottingham,Department of Chemistry
[3] Queen's Medical Centre,Department of Clinical Genetics
[4] Centre for Biochemistry and Cell Biology,undefined
[5] University of Nottingham,undefined
[6] Queen's Medical Centre,undefined
[7] MRC UK HGMP Resource Centre,undefined
[8] School of Chemistry,undefined
[9] University of Nottingham,undefined
[10] University of York,undefined
[11] University of York,undefined
[12] Royal Hospital for Sick Children,undefined
[13] Departement de Pediatrie,undefined
[14] INSERM U-393,undefined
[15] Hopital des Enfants-Malades,undefined
[16] Service de Cardiologie Pediatrique,undefined
[17] Hopital des Enfants-Malades,undefined
[18] MRC geneservice,undefined
[19] Babraham Bioincubator,undefined
[20] Centro Nacional de Investigaciones Oncologicas,undefined
[21] PITO,undefined
来源
Nature Genetics | 2005年 / 37卷
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摘要
Atrial septal defect is one of the most common forms of congenital heart malformation. We identified a new locus linked with atrial septal defect on chromosome 14q12 in a large family with dominantly inherited atrial septal defect. The underlying mutation is a missense substitution, I820N, in α-myosin heavy chain (MYH6), a structural protein expressed at high levels in the developing atria, which affects the binding of the heavy chain to its regulatory light chain. The cardiac transcription factor TBX5 strongly regulates expression of MYH6, but mutant forms of TBX5, which cause Holt-Oram syndrome, do not. Morpholino knock-down of expression of the chick MYH6 homolog eliminates the formation of the atrial septum without overtly affecting atrial chamber formation. These data provide evidence for a link between a transcription factor, a structural protein and congenital heart disease.
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页码:423 / 428
页数:5
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