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 language | English (US) |
|---|---|
| Pages (from-to) | 242-251 |
| Number of pages | 10 |
| Journal | American Journal of Human Genetics |
| Volume | 77 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 2005 |
| Externally published | Yes |
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.