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General Information
Name
CEDNIK syndrome
FlyBase ID
FBhh0000215
Disease Ontology Term
Parent Disease
Overview

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]

Disease Summary Information
Disease Summary: CEDNIK syndrome
OMIM report

[CEREBRAL DYSGENESIS, NEUROPATHY, ICHTHYOSIS, AND PALMOPLANTAR KERATODERMA SYNDROME](https://omim.org/entry/609528)

Human gene(s) implicated

[SYNAPTOSOMAL-ASSOCIATED PROTEIN, 29-KD; SNAP29](https://omim.org/entry/604202)

Symptoms and phenotype

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 OMIM:609528, 2016.03.14]

Genetics

CEDNIK syndrome is caused by homozygous mutation in the SNAP29 gene. [from OMIM:609528, 2016.03.14]

Cellular phenotype and pathology

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 OMIM:609528, 2016.03.14]

Molecular information

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]

External links
Disease synonyms
cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome
Search term: endolysosomal trafficking
Search term: lysosomal-autophagy pathway
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    One to one: 1 human to 1 Drosophila.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      Synaptosomal-associated protein 29kDa (Snap29) encodes a member of the SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein (SNAP) receptor) family. It is involved in regulation of autophagy, endocytic recycling and cell division. [Date last reviewed: 2018-10-18]
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      Ortholog of human SNAP29 (1 Drosophila to 1 human).

      Dmel\Snap29 shares 32% identity and 52% similarity with human SNAP29.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (34 groups)
        protein-protein
        Interacting group
        Assay
        References
        anti bait coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based, pull down, western blot
        experimental knowledge based
        experimental knowledge based
        anti tag coimmunoprecipitation, peptide massfingerprinting
        pull down, western blot
        anti bait coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        anti tag coimmunoprecipitation, anti tag western blot
        anti bait coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
        experimental knowledge based
        experimental knowledge based, pull down, western blot
        experimental knowledge based
        experimental knowledge based
        anti bait coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        anti bait coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
        anti bait coimmunoprecipitation, western blot, peptide massfingerprinting, experimental knowledge based, pull down
        anti bait coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
        experimental knowledge based
        anti bait coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
        experimental knowledge based
        anti tag coimmunoprecipitation, western blot, experimental knowledge based, anti tag western blot
        experimental knowledge based, anti bait coimmunoprecipitation, western blot, pull down
        experimental knowledge based, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot, pull down, molecular weight estimation by staining
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based, anti bait coimmunoprecipitation, peptide massfingerprinting
        experimental knowledge based
        experimental knowledge based
        Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
        Models Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 1 )
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Selected mammalian transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        References (5)