Congenital heart defect (CHD), also described as congenital heart disease, is the most common type of birth defect; it is thought to have a significant genetic component. Candidate genes identified in a large-scale exome sequencing analysis have been assessed in a fly system using cardiac-targeted gene silencing of orthologous fly genes. Experiments using the Drosophila ortholog CG5013 may support METTL23 as a candidate gene in the development of CHD.
METTL23 encodes a methyl transferase that functions in transcription regulation. There a single orthologous gene in Drosophila, CG5013. The human METTL23 gene has not been introduced into flies.
The fly gene CG5013 has not been well characterized genetically. Targeted knockdown of CG5013 restricted to the developing heart, effected by RNAi, results in 13% lethality prior to the adult stage. Physical interactions of CG5013 have been described; see below and in the CG5013 gene report.
[updated May 2021 by FlyBase; FBrf0222196]
A congenital heart defect is a problem with the structure of the heart; it is the most common type of birth defect. The defects can involve the walls of the heart, the valves of the heart, and the arteries and veins near the heart. They can disrupt the normal flow of blood through the heart: the blood flow can slow down, go in the wrong direction or to the wrong place, or be blocked completely (https://medlineplus.gov/congenitalheartdefects.html).
Defects range from simple, which might cause no problems, to complex, which can cause life-threatening complications. The most serious defects are categorized as critical congenital heart defects (CCHD). CCHD is life threatening and requires intervention in infancy; approximately 18 out of 10,000 babies are born with CCHD (https://www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/PEHDIC/Pages/Newborn-Screening-for-CCHD.aspx).
Genetic causes of congenital heart disease also account for many of the comorbidities seen with increased frequency in congenital heart disease patients, including neurodevelopmental disability, pulmonary disease, arrhythmia, renal disease, heart failure and an increased incidence of malignancy. (Simmons and Brueckner, 2017; pubmed:28872494).
A number of well studied syndromes, including DiGeorge syndrome, Williams-Beuren syndrome, Alagille syndrome, Noonan syndrome, and Holt-Oram syndrome, include congenital heart defect (Pierpont et al., 2007; pubmed:17519398).
Congenital heart defects (CHTD) are among the most common congenital defects, occurring with an incidence of 8/1,000 live births. The etiology of CHTD is complex, with contributions from environmental exposure, chromosomal abnormalities, and gene defects. [from MIM:306955; 2018.11.13]
METTL23 encodes a methyl transferase that functions in transcription regulation. [Gene Cards, METTL23; 2021, METTL23; 2021.05.15]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human METTL23 (1 Drosophila to 1 human). Dmel\CG5013 shares 46% identity and 64% similarity with the human gene.
