A5040438830- Pediatric Hepatobiliary Diseases and Treatments
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- Hepatitis B Virus Studies
- Barrier Structure and Function Studies
- CRISPR and Genetic Engineering
- Genetic and Kidney Cyst Diseases
- Genetics and Neurodevelopmental Disorders
- interferon and immune responses
- Intracerebral and Subarachnoid Hemorrhage Research
- Renal and related cancers
- Trace Elements in Health
- Pregnancy and Medication Impact
- Pancreatic and Hepatic Oncology Research
- Diabetes and associated disorders
- Metabolism and Genetic Disorders
- Liver Diseases and Immunity
- Hepatitis C virus research
- Genomics and Rare Diseases
King's College London
2014-2022
King's College School
2014
Meyer Children's Hospital
2011
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 stillbirth. Previous studies have reported mutations in hepatocellular transporters (ABCB4, ABCB11). High throughput sequencing 147 patients was performed the ABCB4, ABCB11, ATP8B1, ABCC2 tight junction protein 2 (TJP2). Twenty-six potentially damaging variants were identified following...
Potential conflict of interest: Dr. Thompson is employed by, owns stock in, on the speakers' bureau of, and received grants from Shire. This work was partially supported by a grant to S.E.P. (NHGRI/NCI U01HG006485). Mutations in TJP2 (also named ZO‐2), encoding tight‐junction protein 2 (TJP2), cause an autosomal‐recessive form progressive intrahepatic cholestasis.1 Association deficiency with hepatocellular carcinoma (HCC) childhood has not been recognized. Case Reports Patient 1 A...
Progressive familial intrahepatic cholestasis is a clinical description of phenotype, which we now realize has several different genetic aetiologies. The identification the underlying defects helped to elucidate important aspects liver physiology. latest addition this family diseases tight junction protein 2 (TJP2) deficiency. This also known as zona occludens (ZO-2). patients, so far presented, all have homozygous, protein-truncating mutations. A complete absence was demonstrated. These...
Although a number of genetic forms cholestasis have been identified, the etiology disease remains unidentified in subset patients.Whole exome sequencing (WES) was performed DNA from patients diagnosed with cholestasis, at different points on continuum progressive familial intrahepatic to benign recurrent whom no mutations known genes had identified. Candidate were then assessed larger patient sample, by targeted next-generation (NGS). Disease features presentation and follow-up collected...
The truncating mutations in tight junction protein 2 (TJP2) cause progressive cholestasis, liver failure, and hepatocyte carcinogenesis. Due to the lack of effective model systems, there are no targeted medications for pathology with TJP2 deficiency. We leveraged technologies patient-specific induced pluripotent stem cells (iPSC) CRISPR genome-editing, we aim establish a disease which recapitulates phenotypes patients