The Phenotypic and Genotypic Spectra of Ichthyosis With Confetti Plus Novel Genetic Variation in the 3′ End ofKRT10

Abstract

We present for the first time to our knowledge the spectrum of clinical variability of IWC in 6 patients with confirmed mutations in KRT10. From this, we have extracted major and minor criteria to aid early and correct clinical diagnosis. Ectodermal malformations, present in all patients, suggest a novel classification of IWC as a syndrome. There is remarkable genetic variation at the IWC disease locus within control individuals from the general population.

Arginine‐ but not alanine‐rich carboxy‐termini trigger nuclear translocation of mutant keratin 10 in ichthyosis with confetti

“…This combined product (pUC‐K10) was inserted into the SacI and HindIII restriction sites of p2_wt_c_GFP, exchanging cDNA between mid of exon 1 to 3′‐UTR for a complete gDNA sequence. This wild‐type gDNA construct (p1_wt_g_GFP) contained a common 12 bp deletion in exon 7 (rs778613907) enabling it to be distinguished from endogenous KRT10 of NKc21. The IWC100 variant (c.1373+1delG) (p4_var_g_GFP) was inserted via site‐directed mutagenesis (GenScript ® ).…”

“…The disease is characterized by the appearance of numerous patches of pale, healthy‐appearing skin in most patients during childhood. These increase in size and number with age . Currently, 57 patients from 40 families (49% male, 51% female) have been reported (Table ).…”

Revertant mosaicism in genodermatoses

“…Unlike the few, scattered patches found in the EB, revertant macules and patches in IWC often number in the hundreds to thousands, representing a remarkable frequency of reversion; further, these patches expand in both size and number with age, demonstrating enhanced competitive potential against neighboring lesional cells [42]. In addition to confetti macules, patients also demonstrate dorsal acral hypertrichosis, mammillae hypoplasia, and malformation of the ears [43,44]. …”

Predictive phenotyping of inherited ichthyosis by next‐generation DNA sequencing

“…IWC, also referred to as congenital reticular ichthyosiform erythroderma or ichthyosis variegata, is a nonsyndromic form of ichthyosis resulting from heterozygous mutations in KRT10 or, more recently, KRT1 . Originally described in 1984, approximately only 40 cases have been reported .…”

“…Originally described in 1984, approximately only 40 cases have been reported . The disease manifests at birth with erythroderma and scaling, or sometimes a collodion membrane, and is characterized by the gradual development of numerous confetti‐like spots of normal skin . Some cases of IWC have also been reported with developmental delay, ear deformities, hypoplastic mammary tissue and focal hypertrichosis, although whether these are true disease associations is uncertain.…”