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Genodermatoses: A Full-Color Clinical Guide to Genetic Skin Disorders
by Joel L. Spitz, Vaune J. Hatch
Specially designed for dermatologists, pediatricians, and family physicians
this user-friendly guide to genetic skin disorders is an ideal resource for
both board preparation and clinical practice. To help make learning a difficult
subject more efficient and effective, the text takes a user-friendly, visual approach,
featuring more than 300 full-color
illustrations and a format designed for maximum retention of content.
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Table of Contents:
Disorders of cornification,
Disorders of pigmentation,
Disorders of vascularization,
Disorders of connective tissue,
Disorders with malignant potential,
Epidermolysis bullosa,
Disorders of porphyrin metabolism,
Disorders with photosensitivity,
Disorders with immunodeficiency,
Disorders of hair and nails,
Disorders of metabolism,
Disorders with chromosome abnormalities,
Disorders with short stature
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Research Articles:
Genetic linkage of recessive dystrophic epidermolysis bullosa to the type VII collagen gene
by A Hovnanian, P Duquesnoy, C Blanchet-Bardon, R G Knowlton, S Amselem, M Lathrop, L Dubertret, J Uitto, and M Goossens
Generalized mutilating recessive dystrophic epidermolysis bullosa (RDEB) is
characterized by extreme skin fragility owing to loss of dermal-epidermal adherence.
Immunohistochemical studies have implicated type VII collagen, the major component of
anchoring fibrils, in the etiology of RDEB. In this study, we demonstrate genetic linkage
of the type VII collagen gene and the generalized mutilating RDEB phenotype. We first
identified a Pvull polymorphic site by digestion of an amplified product of the type VII
collagen gene, which was shown to reside within the coding region. Genetic linkage analysis
between this marker and the RDEB phenotype in 19 affected families which were informative
for this polymorphism showed no recombination events, and gave a maximum lod score of 3.97
at a recombination fraction (theta) of 0, demonstrating that this DNA region is involved
in this form of RDEB. These data provide strong evidence that the type VII collagen gene,
which has also been linked with the dominant form of the disease, harbors the mutation(s)
causing the generalized mutilating form of RDEB in these families, thus underscoring the
major functional importance of type VII collagen in basement membrane zone stability.
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Identification and dissection of an enhancer controlling epithelial gene expression in skin
by Satrajit Sinha and Elaine Fuchs
Keratins 14 and 5 are the structural hallmarks of the basal keratinocytes of the epidermis
and outer root sheath (ORS) of the hair follicle. Their genes are controlled in a tissue-specific
manner and thus serve as useful tools to elucidate the regulatory mechanisms involved in
keratinocyte-specific transcription. Previously we identified several keratinocyte-specific
DNase I hypersensitive sites (HSs) in the 5? regulatory sequences of the K14 gene and showed
that a 700-bp regulatory domain encompassing HSs II and III can confer epidermal
and ORS-specific gene expression in transgenic mice in vivo. Although HS II harbored
much of the transactivation activity in vitro, it was not sufficient to restrict expression
to keratinocytes in vivo. We now explore the HS III regulatory element. Surprisingly, this
element on its own confers gene expression to the keratinocytes of the inner root sheath
(IRS) of the hair follicle, whereas a 275-bp DNA fragment containing both HSs II and III
shifts the expression from the IRS to the basal keratinocytes and ORS in vivo. Electrophoretic
mobility-shift assays and mutational studies of HSs III reveal a role for CACCC-box
binding proteins, Sp1 family members, and other factors adding to the list of previously
described factors that are involved in keratinocyte-specific gene expression.
These studies highlight a cooperative interaction of the two HSs domains and
strengthen the importance of combinatorial play of transcription factors that
govern keratinocyte-specific gene regulation.
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