This report describes CEDNIK syndrome, which exhibits autosomal recessive inheritance. The human gene implicated in this disease is SNAP29, which encodes the SNARE protein synaptosome associated protein 29kDa, a protein involved in multiple membrane trafficking steps. There is one identified fly ortholog, Dmel\Snap29, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical amorphic alleles have been generated.
The human SNAP29 gene has not been introduced into flies.
Use of somatic clones in the developing eye disc has allowed characterization of an amorphic Dmel\Snap29 mutation at cellular and tissue levels. Developing imaginal tissue lacking Snap29 exhibits epithelial architecture defects and accumulates large amounts of autophagosomes; fusion of autophagosomes to lysosomes appears to be blocked. Genetic and many physical interactions have been described for Dmel\Snap29; see below and in the Snap29 gene report.
[updated Jul. 2019 by FlyBase; FBrf0222196]
[CEREBRAL DYSGENESIS, NEUROPATHY, ICHTHYOSIS, AND PALMOPLANTAR KERATODERMA SYNDROME; CEDNIK](https://omim.org/entry/609528)
[SYNAPTOSOMAL-ASSOCIATED PROTEIN, 29-KD; SNAP29](https://omim.org/entry/604202)
CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma) syndrome refers to a unique constellation of clinical manifestations including microcephaly, severe neurologic impairment, psychomotor retardation, failure to thrive, and facial dysmorphism, as well as palmoplantar keratoderma and late-onset ichthyosis. Brain magnetic resonance imaging (MRI) shows various degrees of cerebral dysgenesis including absence of corpus callosum and cortical dysplasia. The syndrome has been found to be uniformly fatal between the ages of 5 and 12 years (Fuchs-Telem et al., 2011, pubmed:21073448). [from MIM:609528, 2016.03.14]
CEDNIK syndrome is caused by homozygous mutation in the SNAP29 gene. [from MIM:609528, 2016.03.14]
Skin biopsy from CEDNIK syndrome patients showed clear vesicles in the spinous, granular, and stratum corneum layers, with retained glucosylceramides, suggesting abnormal lamellar granule maturation. These findings indicate that this neurocutaneous syndrome results from abnormal vesicle trafficking, vesicle maturation, and vesicle fusion (Sprecher et al., 2005, pubmed:15968592). [from MIM:609528, 2016.03.14]
SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. SNAP29 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. It also plays a role in ciliogenesis by regulating membrane fusions. [From UniProt, uniprot:O95721 2016.03.14]
One to one: 1 human to 1 Drosophila.
Ortholog of human SNAP29 (1 Drosophila to 1 human).
Dmel\Snap29 shares 32% identity and 52% similarity with human SNAP29.
