A5007031582- Pediatric Hepatobiliary Diseases and Treatments
- Drug Transport and Resistance Mechanisms
- Gallbladder and Bile Duct Disorders
- Liver Disease Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- Neonatal Health and Biochemistry
- Genetic and Kidney Cyst Diseases
- Biochemical and Molecular Research
- Genomics and Rare Diseases
- Genetic factors in colorectal cancer
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Metabolism and Genetic Disorders
- Cellular transport and secretion
- Regulation of Appetite and Obesity
- Diabetes and associated disorders
- Stress Responses and Cortisol
- Aldose Reductase and Taurine
- RNA modifications and cancer
- Amino Acid Enzymes and Metabolism
- Connective tissue disorders research
Children's Hospital of Fudan University
2019-2024
Jinshan Hospital of Fudan University
2022
University of Victoria
2022
Genome British Columbia
2022
Occupational Cancer Research Centre
2022
Center for Digestive and Liver Diseases
2020
To assess the spectrum of pediatric clinical phenotypes in TJP2 disease, we reviewed records our seven patients whom intrahepatic cholestasis was associated with biallelic variants (13; 12 novel) and correlated manifestations mutation type. The effect a splicing variant analyzed minigene assay. effects three missense were protein expression vitro. Our had both remitting persistent cholestasis. Three exhibited growth retardation. Six responded to treatment cholestyramine, ursodeoxycholic...
Background For many children with intrahepatic cholestasis and high-serum gamma-glutamyl transferase (GGT) activity, a genetic aetiology of hepatobiliary disease remains undefined. We sought to identify novel genes mutated in idiopathic high-GGT cholestasis, clinical, histopathological functional correlations. Methods assembled cohort 25 undiagnosed without clinical features biliary-tract infection or radiological choledochal malformation, sclerosing cholangitis cholelithiasis. Mutations...
Familial glucocorticoid deficiency type 1 (FGD1) is an autosomal recessive disorder caused by mutations in melanocortin 2 receptor (MC2R) gene, characterized low or undetectable serum cortisol level and high adrenocorticotropic hormone (ACTH) level. Clinical manifestations include hypoglycemia, seizure, skin hyperpigmentation, hyperbilirubinemia, cholestasis,and tall stature. Some dysmorphic features such as, prominent forehead, hypertelorism, broad nasal bridge, small tapering fingers, have...
Neuroblastoma amplified sequence (NBAS)-associated disease has a wide phenotypic spectrum, including infantile liver failure syndrome type 2 (ILFS2, OMIM #616483), short stature with optic nerve atrophy and Pelger-Huët anomaly (SOPH) (OMIM #614800), combined phenotype overlapping ILFS2 SOPH syndrome. The mutation spectra of NBAS its genotype-phenotype correlation among Chinese were not clear.Clinical genetic data retrospectively collected from the medical charts patients biallelic mutations,...
ABCB11 deficiency presenting in infancy is believed generally to manifest as persistent/progressive cholestasis. We describe a group of patients with biallelic variants whose disorder manifested transient neonatal cholestasis (TNC).Neonatal intrahepatic 68 children (31 males) predictedly pathogenic (PPV) was classified (TNC group, n = 23, 11 males), intermittent (benign recurrent [BRIC] 3, 1 male) or persistent/ progressive (progressive familial [PFIC] 42, 19 males). Clinical, genetic and...
Biallelic pathogenic variants in neuroblastoma-amplified sequence (NBAS) cause a pleiotropic multisystem disorder. Three clinical subgroups have been defined correlating with the localisation of NBAS gene: affecting C-terminal region result SOPH syndrome (short stature, optic atrophy, Pelger-Huët anomaly), Sec 39 domain are associated infantile liver failure type 2 (ILFS2) and ß-propeller give rise to combined phenotype. However, there is still unexplained phenotypic diversity across three...
Abstract Background Clinical studies on progressive familial intrahepatic cholestasis (PFIC) type 5 caused by mutations in NR1H4 are limited. Methods New patients with biallelic variants from our center and all literature were retrospectively analyzed. Results Three new identified to be carrying five variants. Liver phenotypes of manifests as low-γ-glutamyl transferase cholestasis, liver failure related complications. One patient underwent transplantation (LT) survived, two other died...
Abstract Background Infantile liver failure syndrome type 1 (ILFS1, OMIM #615,438), caused by leucyl-tRNA synthase ( LARS1 , *151,350) deficiency, is a rare autosomal-recessive disorder. The clinical manifestations, molecular-genetic features, and prognosis of disease remain largely elusive. Methods Three new instances ILFS1 with confirmed variants in encoding LARS1, were identified. Disease characteristics summarized together those 33 reported cases. Kaplan-Meier analysis was performed to...
Alagille syndrome (ALGS) type 2 caused by mutations in NOTCH2 has genotypic and phenotypic heterogeneity. Diagnosis some atypical patients with isolated hepatic presentation could be missed.Using 2087 paediatric liver manifestations, allele frequencies, in-silico prediction, protein domains clinical features were analysed to define the pathogenicity of variants for diagnosis ALGS 2.Among significantly more absent gnomAD elevated γ-glutamyltransferase (GGT) (p = .041). Significantly which...
Background and AimsWe asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4-mutated patients evaluated prognostic value taurine-conjugated tetrahydroxylated (tauro-THBA) in cholestasis.
Abstract TMEM67 (mecklin or MKS3) locates in the transition zone of cilia. Dysfunction disrupts cilia‐related signaling and leads to developmental defects multiple organs humans. Typical autosomal recessive cause partial overlapping phenotypes, including abnormalities brain, eyes, liver, kidneys, bones, so forth. However, emerging reports isolated nephronophthisis suggest possibility a broader phenotype spectrum. In this study, we analyzed genetic data cholestasis patients with no obvious...
Biallelic MYO5B variants have been associated with familial intrahepatic cholestasis (FIC) low serum gamma-glutamyltransferase (GGT). Intronic or synonymous outside of canonical splice sites (hereinafter referred to as noncanonical variants) uncertain significance were identified in posing a challenge clinical interpretation. This study is aimed at assessing the effects these on premessenger RNA (pre-mRNA) splicing improve recognition pathogenic spliceogenic and better characterize genetic...
Abstract The liver manifestations of Alagille syndrome (ALGS) are highly variable, and factors affecting its prognosis poorly understood. We asked whether or not the composition bile acids in ALGS patients with good clinical outcomes differs from those poor outcomes, could be used as prognostic biomarkers. Blood for acid profiling were collected genetically confirmed JAG1 -associated before one year age. Good was defined survival native total bilirubin (TB) < 85.5 µmol/L, while either...