Publications by authors named "Melissa Sambrotta"
Article Synopsis
- Researchers are studying liver disease caused by mutations in the TJP2 gene, which leads to serious health issues like liver failure and cancer.
- They created a model using induced pluripotent stem cells (iPSC) and CRISPR technology to mimic the disease symptoms found in affected patients.
- The study found that the iPSC-derived hepatocytes showed disrupted cell structures and impaired bile acid transport, closely resembling the conditions of individuals with TJP2 deficiency, paving the way for future drug development and research.
Article Synopsis
- The study aimed to use next generation sequencing (NGS) to identify genetic causes of unexplained acute liver failure (ALF) in children under 10 admitted to a London hospital.
- Out of 41 children tested, 20% had genetic variants linked to ALF, while 100% of the 4 children undergoing exome sequencing had identifiable variants, with the most common genes being NBAS and those related to mitochondrial DNA.
- Children with genetic variants were younger at presentation and had a higher mortality rate (75% vs 97% survival) compared to those without, suggesting that NGS could enhance diagnosis and treatment strategies for ALF in pediatric patients.
Objectives: Although a number of genetic forms of cholestasis have been identified, the genetic etiology of disease remains unidentified in a subset of cholestasis patients.
Methods: Whole exome sequencing (WES) was performed in DNA from patients diagnosed with cholestasis, at different points on the continuum from progressive familial intrahepatic cholestasis to benign recurrent intrahepatic cholestasis, in whom no disease mutations in known cholestasis genes had been identified. Candidate genes were then assessed in a larger patient sample, by targeted next-generation sequencing (NGS).
Intrahepatic cholestasis of pregnancy (ICP) affects 1/140 UK pregnancies; with pruritus, hepatic impairment and elevated serum bile acids. Severe disease is complicated by spontaneous preterm delivery and stillbirth. Previous studies have reported mutations in hepatocellular transporters (ABCB4, ABCB11).
View Article and Find Full Text PDFBackground & Aims: Neonatal sclerosing cholangitis (NSC) is a severe neonatal-onset cholangiopathy commonly leading to liver transplantation (LT) for end-stage liver disease in childhood. Liver biopsy findings histopathologically resemble those in biliary atresia (BA); however, in NSC extrahepatic bile ducts are patent, whilst in BA their lumina are obliterated. NSC is commonly seen in consanguineous kindreds, suggesting autosomal recessive inheritance.
View Article and Find Full Text PDFProgressive familial intrahepatic cholestasis is a clinical description of a phenotype, which we now realize has several different genetic aetiologies. The identification of the underlying genetic defects has helped to elucidate important aspects of liver physiology. The latest addition to this family of diseases is tight junction protein 2 (TJP2) deficiency.
View Article and Find Full Text PDFArticle Synopsis
- Research on cholestasis has revealed that genetic factors play a crucial role in liver function and disease.
- Mutations in the TJP2 gene disrupt protein localization and tight-junction structures, resulting in severe liver complications.
- The study's results differ from previous findings in knockout mice, emphasizing variations in junctional complex redundancy across different organs and species.