Patched mutations and hairy skin patches: A new sign in Gorlin syndrome

Clinical & Molecular Genetics Unit, Institute of Child Health & Great Ormond Street Hospital, London, UK.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 12/2006; 140(23):2625-30. DOI: 10.1002/ajmg.a.31374
Source: PubMed


We report on the occurrence of discrete patches of unusually long pigmented hair on the skin of three patients with Gorlin syndrome from two unrelated families with confirmed heterozygous mutations in the Patched (PTCH) gene. The PTCH protein is a negative regulator of Hedgehog signaling, and the Sonic Hedgehog (SHH)-PTCH pathway is known to play an important role in the formation and cycling of the hair follicle. We believe that the patches represent a genuine physical sign associated with Gorlin syndrome, and discuss molecular mechanisms by which they might arise.

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    ABSTRACT: Skin tissue engineering emerged as an experimental regenerative therapy motivated primarily by the critical need for early permanent coverage of extensive burn injuries in patients with insufficient sources of autologous skin for grafting. With time, the approach evolved toward a wider range of applications including disease modeling. We have established a skin-humanized mouse model system consisting in bioengineered human-skin-engrafted immunodeficient mice. This new model allows to performing regenerative medicine, gene therapy, genomics, and pathology studies in a human context on homogeneous samples. Starting from skin cells (keratinocytes and fibroblasts) isolated from normal donor skin or patient's biopsies, we have been able to deconstruct-reconstruct several inherited skin disorders including genodermatoses and cancer-prone diseases in a large number of skin humanized mice. In addition, the model allows conducting studies in normal human skin to gain further insight into physiological processes such as wound healing or UV-responses.
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