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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antigens, Polyomavirus Transforming / metabolism
-
Biopsy
-
Blotting, Western
-
Brain / abnormalities*
-
Brain Diseases / genetics*
-
Cell Differentiation
-
Cell Proliferation
-
Chromosome Mapping
-
DNA Mutational Analysis
-
Epidermis / metabolism
-
Family Health
-
Female
-
Fibroblasts / cytology
-
Genotype
-
Haplotypes
-
Homozygote
-
Humans
-
Ichthyosis / genetics*
-
Immunohistochemistry
-
Keratoderma, Palmoplantar / genetics*
-
Male
-
Microsatellite Repeats
-
Microscopy, Electron, Transmission
-
Microscopy, Immunoelectron
-
Models, Genetic
-
Mutation*
-
Nervous System Malformations / genetics*
-
Oligonucleotides / genetics
-
Protein Transport
-
Qb-SNARE Proteins
-
Qc-SNARE Proteins
-
Reverse Transcriptase Polymerase Chain Reaction
-
Sequence Analysis, DNA
-
Syndrome
-
Vesicular Transport Proteins / genetics*
Substances
-
Antigens, Polyomavirus Transforming
-
Oligonucleotides
-
Qb-SNARE Proteins
-
Qc-SNARE Proteins
-
SNAP29 protein, human
-
Vesicular Transport Proteins