This report describes congenital heart defect (postulated), RPL13-related. RPL13, a gene encoding a component of the large ribosome, was identified in a search for de novo copy number variations (CNV) associated with heart defects in humans. RPL13 is also associated with spondyloepimetaphyseal dysplasia, Isidor-Toutain type (MIM:113703), a skeletal growth deficiency.
There is a single high-ranking ortholog of RPL13 in Drosophila, RpL13. Multiple alleles have been generated for RpL13, including ones containing tagged overexpression constructs and RNAi targeting constructs.
A UAS construct of the wild-type human Hsap\RPL13 gene has been introduced into flies, but has not been characterized; a stock is available.
Knocking down RpL13 in flies using a heart-specific driver causes most to die during pupal stage. The few adult escapers have a striking 'no heart' phenotype, with no filamentous actin tube structures in the heart region. This phenotype requires the RNAi to be functional during the embryonic stages and in the first larval instar stage, as activating anti-RpL13 RNAi during mid-first instar causes no loss of heart structures. However, knocking down RpL13 in all muscle is lethal earlier (first and second instar), suggesting that RpL13 has other essential functions.
[updated Sep. 2023 by FlyBase; FBrf0222196]
Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. Although babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment. (GHR_condition:critical-congenital-heart-disease, accessed 2020.02.06.)
In human multipotent cardiac progenitor cells (derived from induced pluripotent stem cells), silencing RPL13 causes a reduction in the fraction of cells that differentiate into cardiomyocytes, as well as dysregulating genes related to cell cycle progression and proliferation. (Adapted from Schroeder et al. 2019, FBrf0244564.)
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human RPL13 (1 Drosophila to 1 human). Dmel\RpL13 shares 63% identity and 76% similarity with the human gene.
