Article
Medicine, Research & Experimental
Simona Hankeova, Noemi Van Hul, Jakub Laznovsky, Elisabeth Verboven, Katrin Mangold, Naomi Hensens, Csaba Adori, Elvira Verhoef, Tomas Zikmund, Feven Dawit, Michaela Kavkova, Jakub Salplachta, Marika Sjoqvist, Bengt R. Johansson, Mohamed G. Hassan, Linda Fredriksson, Karsten Baumgartel, Vitezslav Bryja, Urban Lendahl, Andrew Jheon, Florian Alten, Kristina Tear Fahnehjelm, Bjorn Fischler, Jozef Kaiser, Emma R. Andersson
Summary: This study found significant sex differences in spontaneous bleeding events reported by ALGS patients, with more girls than boys experiencing intracranial hemorrhage. Jag1(Ndr/Ndr) mice displayed various vascular defects, and retinography proved to be a non-invasive method to analyze vascular changes in patients.
EMBO MOLECULAR MEDICINE
(2022)
Article
Medical Laboratory Technology
Yiling Shentu, Xiaoxiao Mi, Dong Tang, Yanming Jiang, Ling Gao, Xiaojie Ma, Bing Zhou, Wenjun Yang, Junping Shi, Dixiang Lan, Gongying Chen, Ling Gong
Summary: This case report highlights the clinical and pathological profiles of a 16-year-old female patient with Alagille syndrome caused by a NOTCH2 gene mutation. The patient presented with unique facial features and liver biopsy findings. The case emphasizes the importance of recognizing and treating Alagille patients with NOTCH2 mutations due to their rarity.
CLINICA CHIMICA ACTA
(2021)
Article
Gastroenterology & Hepatology
Zhong-Die Li, Kuerbanjiang Abuduxikuer, Li Wang, Chen-Zhi Hao, Jing Zhang, Meng-Xuan Wang, Li-Ting Li, Yi-Ling Qiu, Xin-Bao Xie, Yi Lu, Jian-She Wang
Summary: Through a study of 2087 pediatric patients with liver manifestations, it was found that NOTCH2 variants were less frequent in patients with elevated gamma-glutamyltransferase (GGT) and were more likely to be located in protein functional domains. When certain types of variants were absent in gnomAD and predicted to be pathogenic by multiple in-silico tools, they were significantly associated with liver manifestations with elevated GGT. Patients with likely-pathogenic (LP) variants had more liver manifestations and extra-hepatic phenotypes compared to patients with likely benign (LB) variants.
LIVER INTERNATIONAL
(2022)
Article
Cell & Tissue Engineering
Floris J. M. Roos, Gilles S. van Tienderen, Haoyu Wu, Ignacio Bordeu, Dina Vinke, Laura Munoz Albarinos, Kathryn Monfils, Sabrah Niesten, Ron Smits, Jorke Willemse, Oskar Rosmark, Gunilla Westergren-Thorsson, Daniel J. Kunz, Maurice de Wit, Pim J. French, Ludovic Vallier, Jan N. M. IJzermans, Richard Bartfai, Hendrik Marks, Ben D. Simons, Martin E. van Royen, Monique M. A. Verstegen, Luc J. W. van der Laan
Summary: Researchers have successfully established human branching cholangiocyte organoids, which can self-organize into complex tubular structures resembling intrahepatic bile ducts. These organoids show high similarity to primary cholangiocytes, and the branching growth process is dependent on JAG1/NOTCH2 signaling. When applied to cholangiocarcinoma tumor organoids, the branching cholangiocarcinoma organoids exhibit morphology and transcriptomic profile closer to primary tumors and increased chemoresistance.
Article
Biology
Ishita Jain, Ian C. Berg, Ayusha Acharya, Maddie Blaauw, Nicholas Gosstola, Pablo Perez-Pinera, Gregory H. Underhill
Summary: This study assesses the interplay between Notch signaling and cellular mechanics by integrating cellular microarrays, experimental and computational data for liver progenitor cell differentiation patterning. The role of Notch signaling in the spatiotemporal regulation of stem and progenitor cell differentiation has been elucidated using controlled in vitro multicellular culture systems. Computational models incorporating Notch ligand-receptor interactions have provided important insights into Notch pathway signaling dynamics. However, the mechanistic relationship between Notch-mediated intercellular signaling and cooperative microenvironmental cues is less clear. This study systematically evaluates the complex interplay of cellular mechanics and Notch signaling in liver progenitor cell differentiation, and suggests a possible role of E-Cadherin in translating intercellular mechanical gradients to downstream Notch signaling.
COMMUNICATIONS BIOLOGY
(2022)
Article
Pediatrics
Fengdan Xu, Qi Peng, Xiaoguang He, Xiaolan Chen, Shuanglan Jiang, Xiaomei Lu, Ning Li
Summary: We report the first case of Alagille syndrome (ALGS) presenting as prenatal oligohydramnios and renal lesions caused by a de novo variant of the NOTCH2 gene. This case expands the spectrum of NOTCH2 gene variants associated with ALGS and highlights the importance of monitoring liver and kidney function in infants with prenatal oligohydramnios.
FRONTIERS IN PEDIATRICS
(2022)
Article
Oncology
Ying-Ming Tsai, Kuan-Li Wu, Yu-Wei Liu, Wei-An Chang, Yung-Chi Huang, Chao-Yuan Chang, Pei-Hsun Tsai, Szi-Hui Liao, Jen-Yu Hung, Ya-Ling Hsu
Summary: This study verified the role of cancer-associated fibroblasts (CAFs) in inducing lung cancer to create vascular-like networks, facilitating tumor development and metastasis. Disruption of the connections between cancer cells and CAFs can enhance the anti-tumor effect of anti-vascular endothelial growth factor antibodies.
FRONTIERS IN ONCOLOGY
(2021)
Editorial Material
Nutrition & Dietetics
Meifen Wang, Zhikuan Cun, Junchao Peng, Rui Chen, Jiwei Li
Summary: Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disease with a very low prevalence. While around 500 similar cases have been reported in the literature, no types of CGL with NOTCH2 gene mutation have been described.
EUROPEAN JOURNAL OF CLINICAL NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Lucia Fadiga, Mariana Lavrador, Nuno Vicente, Luisa Barros, Catarina Goncalves, Asma Al-Naama, Luis R. Saraiva, Manuel C. Lemos
Summary: A novel missense mutation in the FGFR1 gene associated with CHH has been identified, expanding the mutational spectrum of this gene and contributing to the understanding of the pathogenesis of CHH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Mengmeng Lu, Shuai Kong, Mingfei Xiang, Yu Wang, Jingjing Zhang, Zongliu Duan, Xiaomin Zha, Fengsong Wang, Yunxia Cao, Fuxi Zhu
Summary: In this study, a novel homozygous missense mutation of PMFBP1 was identified in an infertile male from a consanguineous family, leading to a significant decrease in expression of the mutant protein in sperm. This mutation may be a cause of acephalic spermatozoa syndrome, providing a basis for genetic counseling for the patient.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2021)
Article
Pediatrics
Yijiang Han, Kun Zhu, Hao Wu, Baohai Chen, Shuqi Hu, Dengming Lai, Jinfa Tou
Summary: This article reports two cases of infants with cholestatic jaundice. Biliary atresia was ruled out through characteristic facial features, serological tests, imaging, laparoscopic cholangiography, pathology, and genetic findings. The final diagnosis was Alagille syndrome, with novel mutations on chromosome 20. The study expands the spectrum of JAG1 gene mutations associated with Alagille syndrome.
FRONTIERS IN PEDIATRICS
(2022)
Article
Genetics & Heredity
Shimriet Zeidler, Lies Anne Severijnen, Helen de Boer, Esmay C. van der Toorn, Claudia A. L. Ruivenkamp, Emilia K. Bijlsma, Rob Willemsen
Summary: Fragile X syndrome (FXS) is a common monogenetic cause of intellectual disability and autism spectrum disorders, usually resulting from FMR1 gene transcriptional silencing. A missense variant in the FMR1 gene was described in a boy with intellectual disability, leading to significant retention of FMRP in the nucleus, potentially affecting its essential functional sites in dendrites and synaptic compartments.
Article
Ophthalmology
Mariana Matioli da Palma, Austin D. Igelman, Cristy Ku, Amanda Burr, Jia Yue You, Emily M. Place, Nan-Kai Wang, Jin Kyun Oh, Kari E. Branham, Xinxin Zhang, Jeeyun Ahn, Michael B. Gorin, Byron L. Lam, Cecinio C. Ronquillo, Paul S. Bernstein, Aaron Nagiel, Rachel Huckfeldt, Michelle T. Cabrera, John P. Kelly, Benjamin Bakall, Alessandro Iannaccone, Robert B. Hufnagel, Wadih M. Zein, Robert K. Koenekoop, David G. Birch, Paul Yang, Abigail T. Fahim, Mark E. Pennesi
Summary: This study aimed to characterize the phenotypic spectrum of ophthalmic findings in patients with Alagille syndrome. It found that cardiovascular abnormalities, hepatobiliary issues, musculoskeletal anomalies, dysmorphic facies, peripheral vision loss, anterior segment abnormalities, optic disc abnormalities, and peripheral retinal abnormalities were common in these patients. It also identified novel JAG1 mutations in some individuals, suggesting the potential for new diagnostic markers for this syndrome.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Natalia Semenova, Elena Kamenets, Eleonora Annenkova, Andrey Marakhonov, Elena Gusarova, Nina Demina, Daria Guseva, Inga Anisimova, Anna Degtyareva, Natalia Taran, Tatiana Strokova, Ekaterina Zakharova
Summary: Alagille syndrome (ALGS) is a condition characterized by cholestasis and bile duct paucity caused by gene mutations. It affects multiple systems and presents with variable clinical features. Genetic testing is essential for accurate diagnosis and differentiation from other types of cholestasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Malte Zorn, Jirko Kuehnisch, Sebastian Bachmann, Wenke Seifert
Summary: This study investigated the pathogenic effect of missense variants in the VPS13B gene on Cohen syndrome through clinical patient information, in silico predictions, and in vitro testing. The study found that 6 out of 10 missense variants were likely pathogenic, providing insights into the pathomechanisms of Cohen syndrome.
SCIENTIFIC REPORTS
(2022)