Multiple molecular diagnoses (MMD) involve distinct or overlapping phenotypes. They are not so rare in the field of congenital anomalies, given an overall 3.5%-8% rate. Mainly, MMD imply distinct genotypes. Exceptionally, genotypes are linked, involving a causal CNV by itself, facing a SNV for a recessive disorder resulting in a dual diagnosis. An unrelated couple was referred at 21 + 3 weeks of gestation for talipes equinovarus, cerebellar hypoplasia, clenched fists, elevated hemidiaphragm, and micrognathia. Chromosomal microarray and exome sequencing analyses were performed. Both identified a pathogenic de novo 22q11.21 deletion (22q11.2del). Fetal autopsy revealed additional features (postaxial polydactyly, facial features, and abnormal lung lobulation), atypical for 22q11.2del syndrome. At the clinician's request, exome sequencing reanalysis identified a paternally inherited SCARF2 variant, in trans to the 22q11.2del causing autosomal recessive Van den Ende-Gupta syndrome. This dual diagnosis explains the entire fetus phenotype. This is a novel case of dual diagnosis, first prenatal and second case of this ultrarare association. It reflects the crucial role of precise phenotypic description, combined with the importance of considering dual diagnosis in case of atypical clinical presentation. Finally, prenatal phenotypes remain a challenge given the paucity of available known prenatal data for most rare diseases. ClinicalTrial.gov ID: NCT05182242.

Scavenger receptors (SRs), a category of pattern recognition receptors primarily expressed on the surface of myeloid cells, play pivotal roles in oxidation response and lipid metabolism. However, current research on Scavenger Receptor class F type II (SRECⅡ) revolves around Van Den Ende-Gupta Syndrome (VDEG), the potential function of SRECII, particularly in regulating lipid metabolism and oxidative stress processes, remains elusive. Herein, we elucidate that SRECII from Epinephelus coioides (EcSRECII) may modulate fatty acid oxidation and oxidative stress levels via interactions with lipoprotein particles. EcSRECII mediates the internalization of oxidized Low-Density Lipoprotein (oxLDL), thereby inducing lipid accumulation. This process upregulates the expression of genes associated with lipid synthesis and concurrently suppresses those involved in lipolysis. Additionally, EcSRECII exacerbates the production of Reactive Oxygen Species (ROS) following oxLDL exposure, evidenced by significantly heightened activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), increased accumulation of malondialdehyde (MDA), and enhanced total antioxidant capacity (T-AOC). Furthermore, we reveal that EcSRECII-mediated oxLDL internalization culminates in apoptosis and necrosis in GS cells. Ultimately, we demonstrate that EcSRECII augments oxLDL-induced cellular oxidative stress and inflammatory responses, effects that are notably mitigated by EcSRECII knockdown or pretreatment with the fatty acid synthase (FAS) inhibitor C75. Collectively, our study underscores the role of EcSRECII in facilitating oxLDL internalization and subsequent lipid metabolism remodeling, thereby participating in the intricate regulation of intracellular oxidative stress and immune responses.

Scavenger Receptor Class F Member 2 (SCARF2), also known as the Type F Scavenger Receptor Family gene, encodes for Scavenger Receptor Expressed by Endothelial Cells 2 (SREC-II). This protein is a crucial component of the scavenger receptor family and is vital in protecting mammals from infectious diseases. Although research on SCARF2 is limited, mutations in this protein have been shown to cause skeletal abnormalities in both SCARF2-deficient mice and individuals with Van den Ende-Gupta syndrome (VDEGS), which is also associated with SCARF2 mutations. In contrast, other scavenger receptors have demonstrated versatile responses and have been found to aid in pathogen elimination, lipid transportation, intracellular cargo transportation, and work in tandem with various coreceptors. This review will concentrate on recent progress in comprehending SCARF2 and the functions played by members of the Scavenger Receptor Family in pre-diagnostic diseases.

Van den Ende-Gupta syndrome (VDEGS) (MIM#600920) is characterized by skeletal and craniofacial abnormalities that include prominent ears, downslanting palpebral fissures, blepharophimosis, hypoplastic maxilla with or without a cleft palate, a narrow and convex nasal bridge and an everted lower lip, camptodactyly and arachnodactyly. Intelligence is normal. Recent studies have reported that patients with VDEGS have pathogenic variants in the SCARF2 gene on chromosome 22q11.21. Here, we report two Turkish patients with two novel variants [c.2291_2292insC (p.Ser765LeufsTer6) and c.488G>A (p.Cys63Tyr)] in the SCARF2 gene. In silico analysis predicted that both of these novel variants were pathogenic. To the best of our knowledge, this is the first case report of this syndrome in Turkey.