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

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

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)242-251
Number of pages10
JournalAmerican Journal of Human Genetics
Volume77
Issue number2
DOIs
StatePublished - Aug 2005
Externally publishedYes

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    Sprecher, E., Ishida-Yamamoto, A., Mizrahi-Koren, M., Rapaport, D., Goldsher, D., Indelman, M., Topaz, O., Chefetz, I., Keren, H., O'Brien, T. J., Bercovich, D., Shalev, S., Geiger, D., Bergman, R., Horowitz, M., & Mandel, H. (2005). 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. American Journal of Human Genetics, 77(2), 242-251. https://doi.org/10.1086/432556