Ching et al. (2005) described a 4-generation family with ASD and no other cardiac abnormalities, or other malformations of any type. All affected individuals had an ASD of the secundum type, defined as an unrestrictive ASD with increased ... Ching et al. (2005) described a 4-generation family with ASD and no other cardiac abnormalities, or other malformations of any type. All affected individuals had an ASD of the secundum type, defined as an unrestrictive ASD with increased right ventricular preload and increased pulmonary blood flow of more than 1.5 times systemic flow according to the Doppler continuity equation. Several individuals had surgical closure of ASD in childhood. No ASD detected in childhood closed spontaneously.
Within the atrial septal defect critical region on chromosome 14q12, Ching et al. (2005) identified MYH6, which is expressed mainly in atrial tissue, as the best candidate gene. They screened the 39 exons of MYH6 in all members ... Within the atrial septal defect critical region on chromosome 14q12, Ching et al. (2005) identified MYH6, which is expressed mainly in atrial tissue, as the best candidate gene. They screened the 39 exons of MYH6 in all members of the family using denaturing high-performance liquid chromatography. Sequencing identified an ile820-to-asn mutation (I820N; 160710.0003) in all affected family members, all obligate carriers, and in 1 other individual, but not in unaffected family members or in 200 chromosomes screened from healthy unrelated individuals. Ching et al. (2005) pointed out that cardiac transcription factor TBX5 (601620) strongly regulates expression of MYH6, but mutant forms of TBX5, which cause Holt-Oram syndrome (HOS; 142900), do not regulate MYH6. Morpholino knockdown of expression of the chick MYH6 homolog eliminated the formation of the atrial septum without overtly affecting atrial chamber formation. These data provided evidence for a link between a transcription factor, a structural protein, and congenital heart disease.