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Your search keyword '"Elizabeth Pohler"' showing total 2 results
Start Over Author "Elizabeth Pohler" Journal nature genetics
2 results on '"Elizabeth Pohler"'

1. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

Author

Reuven Bergman, Ofer Isakov, Akemi Ishida-Yamamoto, Christabelle S M Goh, Andrea Gat, Neil J. Wilson, Michael A. Simpson, Ofer Sarig, Liat Samuelov, Jennifer L. Koetsier, Noam Shomron, Eli Sprecher, W.H. Irwin McLean, Mia Horowitz, Alan D. Irvine, Robert M. Harmon, Sarit Peleg, Debora Rapaport, Kathleen J. Green, John A. McGrath, O. Eytan, Frances J.D. Smith, Ronen Spiegel, Elizabeth Pohler, Shamir Geller, and Ilan Goldberg

Subjects
Male, Allergy, Dermatitis, Biology, medicine.disease_cause, Severity of Illness Index, Article, Pathogenesis, Hypersensitivity, Genetics, medicine, Humans, Netherton syndrome, Wasting Syndrome, Child, Wasting, Barrier function, Mutation, integumentary system, Desmoglein 1, Infant, Syndrome, medicine.disease, Child, Preschool, Immunology, Female, medicine.symptom
Abstract

The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and play a crucial role in maintaining epidermal integrity and barrier function. SAM syndrome-causing mutations resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. The deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect.

Published
2013

2. Haploinsufficiency for AAGAB causes clinically heterogeneous forms of punctate palmoplantar keratoderma

Author

Hiroshi Shimizu, Toshifumi Nomura, Neil J. Wilson, Moez Gribaa, Sébastien Teissier, Alan D. Irvine, Alan Evans, W.H. Irwin McLean, Sara J. Brown, Mohamed Denguezli, Ali Saad, Mohammad Shboul, Ons Mamaï, Christian Cole, Geoffrey J. Barton, M. Zamiri, John A. McGrath, Colin S. Munro, Jennifer Hirst, Patricia J.C. Dopping-Hepenstal, Frances J.D. Smith, Lobna Boussofara, Mitsuhiro Suehiro, Elizabeth Pohler, David Goudie, Benvon Moran, Bruno Reversade, H. M. Horn, Aileen Sandilands, Christabelle S M Goh, Izumi Konohana, Masashi Akiyama, and Other departments

Subjects
Keratinocytes, congenital, hereditary, and neonatal diseases and abnormalities, Haploinsufficiency, Biology, Article, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Cytosol, Genetics, Humans, Epidermal growth factor receptor, skin and connective tissue diseases, 030304 developmental biology, 0303 health sciences, Gene knockdown, Cell growth, Chromosome Mapping, Proteins, Pedigree, Porokeratosis, ErbB Receptors, Adaptor Proteins, Vesicular Transport, Gene Expression Regulation, Cancer research, biology.protein, Carrier Proteins, Punctate palmoplantar keratoderma, HeLa Cells, Protein Binding
Abstract

Palmoplantar keratodermas (PPKs) are a group of disorders that are diagnostically and therapeutically problematic in dermatogenetics(1-3). Punctate PPKs are characterized by circumscribed hyperkeratotic lesions on the palms and soles with considerable heterogeneity. In 18 families with autosomal dominant punctate PPK, we report heterozygous loss-of-function mutations in AAGAB, encoding alpha- and gamma-adaptin binding protein p34, located at a previously linked locus at 15q22. alpha- and gamma-adaptin binding protein p34, a cytosolic protein with a Rab-like GTPase domain, was shown to bind both clathrin adaptor protein complexes, indicating a role in membrane trafficking. Ultrastructurally, lesional epidermis showed abnormalities in intracellular vesicle biology. Immunohistochemistry showed hyperproliferation within the punctate lesions. Knockdown of AAGAB in keratinocytes led to increased cell division, which was linked to greatly elevated epidermal growth factor receptor (EGFR) protein expression and tyrosine phosphorylation. We hypothesize that p34 deficiency may impair endocytic recycling of growth factor receptors such as EGFR, leading to increased signaling and cellular proliferation

Published
2012

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