Palmoplantar keratoderma and erythrokeratodermas

Gene: SNAP29

Comment when marking as ready: 1 Green rating, confirmed DD gene for CEDNIK syndrome (OMIM:609528) plus >3 unrelated cases confirming the association between SNAP29 and CEDNIK syndrome.

Created: 10 Jan 2017, 2:10 p.m.

Comment on list classification: Updated rating from Amber to Green: 1 Green rating plus >3 unrelated cases support the gene:disease association. Confirmed DD gene for CEDNIK syndrome (OMIM:609528).

Created: 10 Jan 2017, 2:09 p.m.

PMID:25958742 (Bel-Salem et al., 2015) report a consanguineous Jordanian family with CEDNIK syndrome, with features including ichthyosis, keratoderma, dysmorphic features and global developmental delay. They identified a homozygous 1bp deletion (c.223delG) in exon 1 of SNAP29 gene in the affected sisters (the mutation was previously reported by Sprecher et al., 2005, PMID:15968592 but with a different numbering). The presence of c.223delG in two unrelated families suggests a possible founder effect in the Arab population but this needs to be formally established via haplotype analysis.

Created: 10 Jan 2017, 2:07 p.m.

In a Pakistani brother and sister with CEDNIK syndrome, Fuchs-Telem et al. (PMID:21073448, 2011) identified homozygosity for a 1-bp insertion (c.486insA) in the SNAP29 gene causing a frameshift predicted to result in premature termination. The mutation was not found in 200 control chromosomes.

Created: 5 Jan 2017, 4:04 p.m.

In affected patients with CEDNIK syndrome (OMIM:609528), Sprecher et al. (PMID:15968592, 2005) identified a 1-bp deletion (220delG) in the SNAP29 gene, resulting in premature termination of the protein. The mutation was not identified in 200 control chromosomes.

Created: 5 Jan 2017, 4:04 p.m.

Comment on mode of inheritance: Mode of inheritance confirmed by OMIM.

Created: 5 Jan 2017, 3:02 p.m.

Comment on publications: 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion disorder. PMID:23231787 (McDonald-McGinn et al., 2013) report three novel mutations in SNAP29 in four unrelated patients. SNAP29 maps to 22q11.2 and this work confirms that the phenotypic variability observed in a subset of patients with 22q11.2DS is due to mutations on the non-deleted chromosome.

Created: 5 Jan 2017, 3:01 p.m.

SNAP29 is a confirmed DD gene for 'Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome' (Cednik Syndrome, OMIM:609528).

Created: 5 Jan 2017, 2:57 p.m.

Green List (high evidence)

Hemizygous mutations unmasking recessive phenotype in 22q11.2 deletion syndrome

Created: 16 Nov 2015, 8:35 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma.

Publications

• 23231787
• 15968592