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 journalArticlepeer-review

165 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
Pages (from-to)242-251
Number of pages10
JournalAmerican Journal of Human Genetics
Volume77
Issue number2
DOIs
StatePublished - Aug 2005
Externally publishedYes

Bibliographical note

Funding Information:
We are grateful to the family members for their participation in our study. We thank Dr. Vered Friedman, for services in nucleic acid analysis; Ma’ayan Fishelson and Anna Tzemach, for computer assistance; and Dr. Peter Itin, Dr. Gabriele Richard, Dr. Eddie Karnieli, Dr. Tsipora Kra-Oz, Alon Hirshberg, and Dr. Gila Maor, for stimulating discussions. This study was supported in part by grants provided by the Ruth and Allen Ziegler Fund for Pediatric Research (to E.S.) and the Japanese Ministry of Education, Culture, Sports, Science and Technology (to A.I.Y.). Electron microscopy samples were observed at the Electron Microscopy Unit, Central Laboratory for Research and Education, Asahikawa Medical College.

Funding

We are grateful to the family members for their participation in our study. We thank Dr. Vered Friedman, for services in nucleic acid analysis; Ma’ayan Fishelson and Anna Tzemach, for computer assistance; and Dr. Peter Itin, Dr. Gabriele Richard, Dr. Eddie Karnieli, Dr. Tsipora Kra-Oz, Alon Hirshberg, and Dr. Gila Maor, for stimulating discussions. This study was supported in part by grants provided by the Ruth and Allen Ziegler Fund for Pediatric Research (to E.S.) and the Japanese Ministry of Education, Culture, Sports, Science and Technology (to A.I.Y.). Electron microscopy samples were observed at the Electron Microscopy Unit, Central Laboratory for Research and Education, Asahikawa Medical College.

FundersFunder number
Ruth and Allen Ziegler Fund for Pediatric Research
Ministry of Education, Culture, Sports, Science and Technology

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