Patau Syndrome (Trisomy 13)
congenital heart problems
Trisomy 18 (Edward's Syndrome)
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
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AbstractThis presentation is part of the PEER Liberia Pediatrics Lecture Series. It provides an overview for physicians of the diagnosis and treatment of congenital diseases and abnormalities, including Down Syndrome, Klinefelter’s Syndrome, Patau Syndrome (Trisomy 13), Turner Syndrome, congenital heart problems, and Trisomy 18 (Edward's Syndrome).
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/36404
Presented online to the ELWA Family Medicine residents, Monrovia, Liberia, on April 20, 2022.
RightsCopyright 2022 The Author(s)
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Hierarchical regulation of WASP/WAVE proteinsPadrick, Shae B.; Cheng, Hui-Chun; Ismail, Ayman M.; Panchal, Sanjay C.; Doolittle, Lynda K.; Kim, Soyeon; Skehan, Brian M.; Umetani, Junko; Brautigam, Chad A.; Leong, John M.; et al. (2008-11-11)Members of the Wiskott-Aldrich syndrome protein (WASP) family control actin dynamics in eukaryotic cells by stimulating the actin nucleating activity of the Arp2/3 complex. The prevailing paradigm for WASP regulation invokes allosteric relief of autoinhibition by diverse upstream activators. Here we demonstrate an additional level of regulation that is superimposed upon allostery: dimerization increases the affinity of active WASP species for Arp2/3 complex by up to 180-fold, greatly enhancing actin assembly by this system. This finding explains a large and apparently disparate set of observations under a common mechanistic framework. These include WASP activation by the bacterial effector EspFu and a large number of SH3 domain proteins, the effects on WASP of membrane localization/clustering and assembly into large complexes, and cooperativity between different family members. Allostery and dimerization act in hierarchical fashion, enabling WASP/WAVE proteins to integrate different classes of inputs to produce a wide range of cellular actin responses.
Attaching-and-Effacing Pathogens Exploit Junction Regulatory Activities of N-WASP and SNX9 to Disrupt the Intestinal BarrierGarber, John J.; Mallick, Emily M.; Scanlon, Karen M.; Turner, Jerrold R.; Donnenberg, Michael S.; Leong, John M.; Snapper, Scott B. (2017-12-15)Background and Aims: Neural Wiskott-Aldrich Syndrome protein (N-WASP) is a key regulator of the actin cytoskeleton in epithelial tissues and is poised to mediate cytoskeletal-dependent aspects of apical junction complex (AJC) homeostasis. Attaching-and-effacing (AE) pathogens disrupt this homeostasis through translocation of the effector molecule early secreted antigenic target-6 (ESX)-1 secretion-associated protein F (EspF). Although the mechanisms underlying AJC disruption by EspF are unknown, EspF contains putative binding sites for N-WASP and the endocytic regulator sorting nexin 9 (SNX9). We hypothesized that N-WASP regulates AJC integrity and AE pathogens use EspF to induce junction disassembly through an N-WASP- and SNX9-dependent pathway. Methods: We analyzed mice with intestine-specific N-WASP deletion and generated cell lines with N-WASP and SNX9 depletion for dynamic functional assays. We generated EPEC and Citrobacter rodentium strains complemented with EspF bearing point mutations abolishing N-WASP and SNX9 binding to investigate the requirement for these interactions. Results: Mice lacking N-WASP in the intestinal epithelium showed spontaneously increased permeability, abnormal AJC morphology, and mislocalization of occludin. N-WASP depletion in epithelial cell lines led to impaired assembly and disassembly of tight junctions in response to changes in extracellular calcium. Cells lacking N-WASP or SNX9 supported actin pedestals and type III secretion, but were resistant to EPEC-induced AJC disassembly and loss of transepithelial resistance. We found that during in vivo infection with AE pathogens, EspF must bind both N-WASP and SNX9 to disrupt AJCs and induce intestinal barrier dysfunction. Conclusions: Overall, these studies show that N-WASP critically regulates AJC homeostasis, and the AE pathogen effector EspF specifically exploits both N-WASP and SNX9 to disrupt intestinal barrier integrity during infection.
The phakomatoses: dermatologic clues to neurologic anomaliesNowak, Catherine Bearce (2007-09-06)The phakomatoses of particular interest to neurologists including Sturge-Weber syndrome, neurofibromatosis type 1, neurofibromatosis type 2, Bannayan-Riley-Ruvalcaba syndrome, and Proteus syndrome are presented. The physical manifestations required for clinical diagnosis, the neurologic features, and recommendations for management are given. The molecular etiology and genetic aspects of these disorders are briefly discussed as well as future implications of on-going research.