Alu‐mediated large deletion of the CDSN gene as a cause of peeling skin disease

Abstract

Peeling skin disease (PSD) is an autosomal recessive skin disorder caused by mutations in CDSN and is characterized by superficial peeling of the upper epidermis.Corneodesmosin (CDSN) is a major component of corneodesmosomes that plays an important role in maintaining epidermis integrity. Herein, we report a patient with PSD caused by a novel homozygous large deletion in the 6p21.3 region encompassing the CDSN gene, which abrogates CDSN expression. Several genes including C6orf15, PSORS1C1, PSORS1C2, CCHCR1, and TCF19 were also deleted, however, the patient showed only clinical features typical of PSD. The deletion size was 59.1 kb. Analysis of the sequence surrounding the breakpoint showed that both of the telomeric and centromeric breakpoints existed within Alu-S sequences that were oriented in opposite directions. These results suggest an Alu-mediated recombination event as the mechanism underlying the deletion in our patient.

Phylogenetic profiling and gene expression studies implicate a primary role of PSORS1C2 in terminal differentiation of keratinocytes

“…Thus, the loss of functional PSORS1C2 in cetaceans is in line with the loss of this programme. In humans, homozygous deletions of six different genes including CDSN and PSORS1C2 are associated with generalized peeling skin disease . As the inactivation of CDSN alone is sufficient to induce peeling skin disease, these clinical cases are not informative about the role of PSORS1C2 , as the latter may be obscured by the effects of lack of CDSN .…”

Genes involved in keratinization, keratinocyte and epithelium differentiation are aberrantly regulated in oral lichen planus

“…Reportedly, CDSN, LCEs, and SPRR2B are all part of the epidermal differentiation complex (EDC) (Gudjonsson et al 2009;Danielsson et al 2014). Corneodesmosin (CDSN) is a major component of corneodesmosomes, which localize to cornified human squamous epithelia and play an important role in maintaining epidermis integrity (Wada et al 2014). LCE3D (late cornified envelope 3D) and LCE3E (late cornified envelope 3E) belong to LCE family encoding structural proteins in terminally differentiated keratinocytes (Jackson et al 2005;Hoss et al 2013).…”

Increased expression of epidermal thymic stromal lymphopoietin in inflammatory peeling skin syndrome

“…Linear punctate PPK can be seen in all races and its rates are the same in both sexes. 4 Generally, it is seen between the ages of 10-30 years. [1][2][3]…”

“…Although allergen-specific IgE were initially all negative, the patient was sensitized with multiple inhalant and food allergens with age. 4 Eosinophil counts were gradually decreased after improvement of the initial skin lesions. The patient developed IgE-mediated fish allergy and atopic dermatitis.…”

“…Her clinical and pathophysiological data have been reported elsewhere. 4 She developed generalized erythematous rash immediately after birth, followed by superficial peeling and ichthyosiform erythroderma. Laboratory studies revealed marked eosinophilia and a rapid elevation of total serum immunoglobulin (Ig)E levels during early infancy (Fig.…”