A mutation in SNAP29, coding for a SNARE protein involved in intracellular trafficking, causes a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma.

نویسندگان

  • Eli Sprecher
  • Akemi Ishida-Yamamoto
  • Mordechai Mizrahi-Koren
  • Debora Rapaport
  • Dorit Goldsher
  • Margarita Indelman
  • Orit Topaz
  • Ilana Chefetz
  • Hanni Keren
  • Timothy J O'brien
  • Dani Bercovich
  • Stavit Shalev
  • Dan Geiger
  • Reuven Bergman
  • Mia Horowitz
  • Hanna Mandel
چکیده

Neurocutaneous syndromes represent a vast, largely heterogeneous group of disorders characterized by neurological and dermatological manifestations, reflecting the common embryonic origin of epidermal and neural tissues. In the present report, we describe a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK syndrome). Using homozygosity mapping in two large families, we localized the disease gene to 22q11.2 and identified, in all patients, a 1-bp deletion in SNAP29, which codes for a SNARE protein involved in vesicle fusion. SNAP29 expression was decreased in the skin of the patients, resulting in abnormal maturation of lamellar granules and, as a consequence, in mislocation of epidermal lipids and proteases. These data underscore the importance of vesicle trafficking regulatory mechanisms for proper neuroectodermal differentiation.

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Synaptosomal-associated protein 29 (SNAP29) is a t-SNARE protein that is implicated in intracellular vesicle fusion. Mutations in the SNAP29 gene have been associated with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome (CEDNIK). In patients with 22q11.2 deletion syndrome, mutations in SNAP29 on the nondeleted chromosome are linked to similar ichthyotic and neurological ph...

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عنوان ژورنال:
  • American journal of human genetics

دوره 77 2  شماره 

صفحات  -

تاریخ انتشار 2005