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.
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.
Sprecher
Eli
E
Department of Dermatology and Laboratory of Molecular Dermatology, Rambam Medical Center, Haifa, Israel. e_sprecher@rambam.health.gov.il
Ishida-Yamamoto
Akemi
A
Mizrahi-Koren
Mordechai
M
Rapaport
Debora
D
Goldsher
Dorit
D
Indelman
Margarita
M
Topaz
Orit
O
Chefetz
Ilana
I
Keren
Hanni
H
O'brien
Timothy J
TJ
Bercovich
Dani
D
Shalev
Stavit
S
Geiger
Dan
D
Bergman
Reuven
R
Horowitz
Mia
M
Mandel
Hanna
H
D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D001706:Biopsy; D015153:Blotting, Western; D001921:Brain / Q000002:abnormalities*; D001927:Brain Diseases / Q000235:genetics*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004817:Epidermis / Q000378:metabolism; D005192:Family Health; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007057:Ichthyosis / Q000235:genetics*; D007150:Immunohistochemistry; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D008957:Models, Genetic; D009154:Mutation; D009421:Nervous System Malformations / Q000235:genetics*; D009841:Oligonucleotides / Q000235:genetics; D021381:Protein Transport; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013577:Syndrome; D033921:Vesicular Transport Proteins / Q000235:genetics*
D000952:Antigens, Polyomavirus Transforming; D009841:Oligonucleotides; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C432420:SNAP29 protein, human; D033921:Vesicular Transport Proteins