New Arab family with cerebral dysgenesis, neuropathy, ichthyosis and keratoderma syndrome suggests a possible founder effect for the c.223delG mutation

How to use a multipurpose SNARE: The emerging role of Snap29 in cellular health

“…An association of Snap29 with schizophrenia emerged in two early reports that revealed the presence of a polymorphism in the promoter region of SNAP29 with schizophrenia patients 5748. In addition, a study found the SNAP29 promoter among the many bound by β-catenin, a transcription factor regulated by lithium, an antipsychotic drug 42, and a bioinformatic analysis associated SNAP29 with a schizophrenia gene network 43.…”

“…Indeed, it was reported that loss of SNAP29 cause CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma), a rare recessive congenital syndrome. In CEDNIK patients, homozygous SNAP29 loss of function mutations cause a typical set of neurocutaneous traits that results in very poor life expectancy 4647484950. The alterations due to lack of SNAP29 have been analyzed in the stratum corneum of skin of patients, which presents an accumulation of glucosylceramides normally secreted towards the upper layers, suggesting the existence of a defect in secretion of lamellar granules containing lipids and proteolytic enzymes important for normal skin development.…”

Cednik

“…5,9 Brain magnetic resonance imaging (MRI) of patients with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma shows corpus callosum dysgenesis and cortical dysplasia with pachygyria and polymicrogyria. [5][6][7][8] In line with these observations, animal studies have shown that both total SNAP29 knockout mice and keratinocytespecific knockout mice have neonatal lethality, acanthosis, hyperkeratosis, abnormal keratinocyte differentiation, and increased proliferation. 2 Mutant mice have decreased deposition of lamellar body contents into the epidermis, as shown by their altered epidermal lipid distribution, as well as malformed lamellar bodies and an impaired epidermal barrier.…”

“…3,4 Loss-of-function mutations in SNAP29 have been shown to cause autosomal recessive cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome (CEDNIK). [5][6][7] Moreover, patients with hemizygous deletions of 22q11.2 combined with mutations in the nondeleted SNAP29 display many of the features present in CEDNIK, confirming the lossof-function mechanism. 8 Patients with CEDNIK typically present with ichthyosis (dry, scaly skin), keratoderma (marked thickening of skin, typically of the palms and soles), intellectual disability, microcephaly, facial dysmorphism, hypoplastic optic discs, sensorineural deafness, and cachexia, among other features.…”

CEDNIK syndrome in an Indian patient with a novel mutation of the SNAP29 gene

“…CEDNIK (CErebral Dysgenesis, Neuropathy, Ichthyosis, and Keratoderma) syndrome is a neuroichthyotic syndrome characterized by a constellation of clinical features including severe developmental retardation, microcephaly, and facial dysmorphism. To date, only 12 cases have been reported worldwide . Here, we report the first case of CEDNIK syndrome from India harboring a novel mutation of SNAP29 gene.…”