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Fetus in fetu is a rare congenital anomaly in which a malformed parasitic twin is found within the body of a living child or adult. In this case report, a 1-day-old child presented with a large firm abdominal mass on the left side of the upper abdomen. Imaging studies misdiagnosed the mass as an intraperitoneal benign dermoid cyst displacing the bowel loops and internal viscera. A surgical resection was performed on 21 days of life, and pathology confirmed eight fetuses inside the cyst.
RESUMO
Multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) results from mutations in the phosphatidylinositol glycan biosynthesis class T (PIGT) gene leading to defects in glycosylphosphatidylinositol transamidase complex (GPI-TA) synthesis. Glycosylphosphatidylinositol serves as an anchor to more than 150 mammalian proteins for attachment on cell surfaces, enabling specific functional properties. Mutations in the PIGT gene result in disruption of this extremely important post-translational protein modification, yielding dysfunctional proteins leading to MCAHS3. An exhaustive literature search was conducted across various electronic databases to reveal only 41 reported cases of MCAHS3 worldwide, emphasizing the rarity of this condition. Multiple congenital anomalies-hypotonia-seizures syndrome 3 has been reported as secondary to 18 different known PIGT variants to date, manifesting as a varying spectrum of craniofacial dysmorphism, developmental delay with epilepsy, cardiac and renal malformations, and unique features in biochemical testing and neuroimaging. This review aims to highlight the constellation of clinical symptoms, diagnostic modalities, and management challenges associated with MCAHS3 cases. It would help determine optimal diagnostic and treatment strategies for newly identified cases and facilitate new research on this rare condition.
RESUMO
BACKGROUND: Fasciola spp. liver fluke cause pernicious disease in humans and animals. Whilst current control is unsustainable due to anthelmintic resistance, gene silencing (RNA interference, RNAi) has the potential to contribute to functional validation of new therapeutic targets. The susceptibility of juvenile Fasciola hepatica to double stranded (ds)RNA-induced RNAi has been reported. To exploit this we probe RNAi dynamics, penetrance and persistence with the aim of building a robust platform for reverse genetics in liver fluke. We describe development of standardised RNAi protocols for a commercially-available liver fluke strain (the US Pacific North West Wild Strain), validated via robust transcriptional silencing of seven virulence genes, with in-depth experimental optimisation of three: cathepsin L (FheCatL) and B (FheCatB) cysteine proteases, and a σ-class glutathione transferase (FheσGST). METHODOLOGY/PRINCIPAL FINDINGS: Robust transcriptional silencing of targets in both F. hepatica and Fasciola gigantica juveniles is achievable following exposure to long (200-320 nt) dsRNAs or 27 nt short interfering (si)RNAs. Although juveniles are highly RNAi-susceptible, they display slower transcript and protein knockdown dynamics than those reported previously. Knockdown was detectable following as little as 4h exposure to trigger (target-dependent) and in all cases silencing persisted for ≥25 days following long dsRNA exposure. Combinatorial silencing of three targets by mixing multiple long dsRNAs was similarly efficient. Despite profound transcriptional suppression, we found a significant time-lag before the occurrence of protein suppression; FheσGST and FheCatL protein suppression were only detectable after 9 and 21 days, respectively. CONCLUSIONS/SIGNIFICANCE: In spite of marked variation in knockdown dynamics, we find that a transient exposure to long dsRNA or siRNA triggers robust RNAi penetrance and persistence in liver fluke NEJs supporting the development of multiple-throughput phenotypic screens for control target validation. RNAi persistence in fluke encourages in vivo studies on gene function using worms exposed to RNAi-triggers prior to infection.