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Molecular genetics of the ichthyoses


  • Gabriele Richard

    Corresponding author
    • Thomas Jefferson University, Department of Dermatology & Cutaneous Biology, 233 S. 10th St., BLSB Suite 409, Philadelphia, PA 19107.
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    • Dr. Richard is associate professor of dermatology and genetics and co-director of the Molecular Diagnostic Laboratory of the Department of Dermatology & Cutaneous Biology at the Thomas Jefferson University, Philadelphia, PA. She has over 10 years experience in clinical and molecular genetic studies of ichthyoses and other disorders of cornification. Her research laboratory has elucidated the molecular basis of numerous ichthyoses, palmoplantar keratoderma, and erythrokeratodermas and is a recognized center of research on connexin biology and pathology.


The ichthyoses are a large, clinically, genetically, and etiologically heterogeneous group of disorders of cornification due to abnormal differentiation and desquamation of the epidermis. Although they differ in clinical features, inheritance, and structural and biochemical abnormalities of the epidermis, they often pose a diagnostic challenge. For each of the 12 ichthyoses and related disorders described here, the major disease genes have been identified and genotype–phenotype correlation have begun to emerge. The molecular findings reveal the functional importance and interactions of many different epidermal proteins and metabolic pathways, including major structural proteins (keratins, loricrin), enzymes involved in lipid metabolism (transglutaminase 1, lipoxygenases, fatty aldehyde dehydrogenase, steroid sulfatase, glucocerebrosidase, Δ8-Δ7 sterol isomerase, 3β-hydroxysteroid dehydrogenase), and protein catabolism (LEKTI), peroxisomal transport and processing (Peroxin 7 receptor, Phytanoyl-CoA hydroxylase) and DNA repair (proteins of the transcription repair complex). This review highlights the spectacular advances in the molecular genetics and biology of heritable ichthyoses over the past decade. It illustrates the power of molecular diagnostics for refining disease classification, providing prenatal diagnosis, improving genetic counseling, and clinical management. © 2004 Wiley-Liss, Inc.

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