27 research outputs found
New intragenic and promoter region deletion mutations in FERMT1 underscore genetic homogeneity in Kindler syndrome
Lokalisierte Pityriasis rubra pilaris in der Schwangerschaft: Eine sehr seltene Sonderform mit therapeutischer Herausforderung
Identification of genetic loci associated with different responses to high-fat diet-induced obesity in C57BL/6N and C57BL/6J substrains
CEDNIK syndrome results from loss-of-function mutations in SNAP29
Background CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis and keratoderma) syndrome is a rare genodermatosis which was shown 5 years ago in one family to be associated with a loss-of-function mutation in SNAP29, encoding a member of the SNARE family of proteins. Decrease in SNAP29 expression was found to result in abnormal lamellar granule maturation leading to aberrant epidermal differentiation and ichthyosis.
Objectives To delineate the molecular consequences of disease-causing mutations in SNAP29.
Methods We used direct sequencing, in vitro mutagenesis and three-dimensional organotypic cell cultures.
Results We identified a novel homozygous insertion in SNAP29 (c.486insA) in two sibs presenting with ichthyosis and dysgenesis of the corpus callosum. In vitro transfection experiments indicated that this mutation results in SNAP29 loss-of-function. Further substantiating this notion, we could replicate histological features typical for CEDNIK syndrome in three-dimensional primary human keratinocyte organotypic cell cultures downregulated for SNAP29.
Conclusions The identification of a second mutation in SNAP29 in the present study definitely establishes a causal relationship between defective function of SNAP29 and the pleiotropic manifestations of CEDNIK syndrome. Our present and previous data position SNAP29 as an essential component of the epidermal differentiation machinery
Multiple functions of the SNARE protein Snap29 in autophagy, endocytic, and exocytic trafficking during epithelial formation in Drosophila
Increased epidermal expression and absence of mutations in <i>CARD14 </i>in a series of patients with sporadic pityriasis rubra pilaris
Pityriasis rubra pilaris (PRP; MIM 173200) encompasses a spectrum of rare chronic papulosquamous inflammatory disorders, which have been classified into 6 subtypes(1) . Clinical features include palmoplantar keratoderma and follicular hyperkeratotic papules which coalesce into large, scaly, erythematous plaques, with frequent progression to exfoliative erythroderma. This article is protected by copyright. All rights reserved