This report describes atrial septal defect 4 (ASD4), which is a sub-type of atrial septal defect (ASD); ASD exhibits autosomal dominant inheritance. The human gene implicated in this disease is TBX20, which encodes a T-box transcription factor. There are 2 high-scoring fly orthologs, H15 and mid, for which classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. The two Drosophila orthologs map within 60kb of each other. They exhibit different expression patterns: H15 is more specifically expressed in cardiac tissues, especially in adults; mid is more broadly expressed, including in early embryos.
The human TBX20 gene has not been introduced into flies.
Most animals homozygous for amorphic mutations of Dmel\mid die during late embryogenesis; among other embryonic phenotypes, a partially penetrant heart phenotype is observed. Mutations of Dmel\H15 have not been well characterized. The penetrance of heart morphogenesis defects in embryos observed for RNAi-induced knockdown of mid is increased in an H15 mutant background.
[updated Apr. 2017 by FlyBase; FBrf0222196]
Congenital heart defect characterized by defects of atrial septation; additional heart abnormalities, such as other defects in septation, defects in chamber growth, or insufficiency of the cardiac valves may be present. [from MIM:611363; 2015.12.18]
Atrial septal defect is characterized by a defect in the interatrial septum allowing pulmonary venous return from the left atrium to pass directly to the right atrium. Depending on the size of the defect, this can result in a spectrum of disease; diagnosis may not occur until adulthood. [from Medscape, http://emedicine.medscape.com/article/162914-overview, 2015.12.18]
[ATRIAL SEPTAL DEFECT 4; ASD4](https://omim.org/entry/611363)
[T-BOX TRANSCRIPTION FACTOR 20; TBX20](https://omim.org/entry/606061)
Atrial septal defect with other congenital heart disease but no conduction defects or noncardiac abnormalities. [from MIM:611363; 2015.12.18]
ASD4 is inherited as an autosomal dominant; it is associated with mutations in the TBX20 gene. [from MIM:611363; 2015.12.18]
TBX20 is a member of the T-box family of transcription factors; it has been shown to interact with known cardiac transcription factors. Both long and short isoforms of the Tbx20 protein are produced, differing in the presence or absence of a C-terminal domain (beyond the T-box). [from MIM:606061; 2015.12.18]
One to many: 1 human to 2 Drosophila.
Ortholog of human TBX20 (2 Drosphila to 1 human). Dmel\H15 shares 35% identity and 47% similarity with the human gene. The 2 fly genes differ in expression patterns: H15 is highly expressed in the heart of the adult fly; low levels of expression are observed in late embryos, primarily in the embryonic dorsal vessel.
Ortholog of human TBX20 (2 Drosphila to 1 human). Dmel\mid shares 40% identity and 54% similarity with the human gene. The 2 fly genes differ in expression patterns: mid is expressed in a variety of tissues, including epidermal and neural; among other embryonic structures, expression is observed in the embryonic dorsal vessel.
