Patched mutations and hairy skin patches: A new sign in Gorlin syndrome
ABSTRACT 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.
Article: Hereditary Nonmelanoma Skin Cancer[Show abstract] [Hide abstract]
ABSTRACT: Cutaneous basal and squamous cell carcinomas are among the most frequent malignancies in the white population, with the annual incidence estimates ranging from 1 million to 3.5 million cases in the United States. These tumors can occur either sporadically or in the context of hereditary genodermatoses with cancer predisposition, such as basal cell nevus syndrome, xeroderma pigmentosum, epidermolysis bullosa, or oculocutaneous albinism. Different genes and signaling pathways have been shown to play a central role in the development and growth of these tumors. This article overviews the clinical features, diagnostic criteria, and the most recent data on genetic routes of the major hereditary syndromes predisposed to the development of nonmelanoma skin cancer.Seminars in cutaneous medicine and surgery 12/2012; 31(4):204-10. DOI:10.1016/j.sder.2012.08.005 · 2.40 Impact Factor
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ABSTRACT: . The relationship of mutations in the patched gene PTCH and nevoid basal cell carcinoma (NBCC) or Gorlin syndrome is well established. Animal studies have implicated the hedgehog-patched signalling pathway in neurulation and neural tube defects (NTDs). Spina bifida occulta and bifid vertebrae are well recognized in NBCCS, but there appears to be only one report of open spina bifida. We report a father and two sons with a truncating PTCH mutation and the major features of NBCCS. One son had open thoracic spina bifida and the other had an occipital meningocoele. We believe this to be the first report of cranial NTD in NBCCS and suggest that consideration be given to including PTCH analysis in genetic association studies in NTDs as the hedgehog pathway is integral to normal human neurulation.Clinical Genetics 06/2011; 82(1):71-6. DOI:10.1111/j.1399-0004.2011.01725.x · 3.65 Impact Factor
Conference Paper: Chaotic dynamics of time-delay neural networks[Show abstract] [Hide abstract]
ABSTRACT: A study is made of the nonlinear dynamical properties of a class of recurrent artificial neural networks with time delay that have been proposed in the literature to learn and recognize time-varying input patterns. Their nonlinear dynamics are studied to see if they have the potential to model nonlinear dynamical behavior of biological field potentials such as the electroencephalogram (EEG). It is shown that changing the value of the weights in a periodic fashion causes the output of time-delay neural networks to show a correlation dimension in the EEG rangeNeural Networks, 1990., 1990 IJCNN International Joint Conference on; 07/1990