Mild Recessive Bullous Congenital Ichthyosiform Erythroderma due to a Previously Unidentified Homozygous Keratin 10 Nonsense Mutation

Abstract

We have identified a previously unreported homozygous nonsense mutation p.Cys427X in the keratin 10 (K10) gene (KRT10) in a Turkish girl with recessive bullous congenital ichthyosiform erythroderma (BCIE) showing superficial blistering. p.Cys427X is located upstream of the previously reported homozygous truncation mutation within the same exon 6 causing mRNA decay. Immunohistochemical examination showed a complete absence of K10 protein in the patient's epidermis. The findings of this study suggest that K10 knockout patients show unique clinicopathological features of clinically mild BCIE with blisters occurring within the granular layer. In addition, the unaffected, heterozygous carriers of the mutation indicate that the K10 peptide from one normal allele alone is sufficient for keratin network formation.

Immortalized keratinocytes derived from patients with epidermolytic ichthyosis reproduce the disease phenotype: a usefulin vitromodel for testing new treatments

“…[2][3][4] EI is caused by mutations in the genes encoding keratin 1 (K1), keratin 2 or keratin 10 (K10), expressed in suprabasal epidermal keratinocytes. [2][3][4] EI is caused by mutations in the genes encoding keratin 1 (K1), keratin 2 or keratin 10 (K10), expressed in suprabasal epidermal keratinocytes.…”

Keratin gene mutations in disorders of human skin and its appendages

“…Even though EI is usually autosomal dominantly inherited, recently several reports showed that this disorder can as well be inherited in a recessive way by involving either a donor splice site, termination codon or nonsense mutations [65–67]. A recessive nonsense KRT10 mutation that leads to the loss of K10 expression has been identified in a consanguineous family with a severe EI phenotype, characterized by sparse keratin filaments with amorphous and homogenous-like keratin aggregates [40].…”

“…Recessive EI has a characteristic ultrastructural picture of EI consisting of sparse keratin filaments with a nearly homogenous and amorphous structure of keratin clumps. Other cases of recessive BCIE describes a homozygous nonsense mutation in KRT10, with heterozygous individuals being non-phenotypic carriers thus, clearly demonstrates that a normal K10 allele is sufficient to maintain a normal KIF network [67]. …”

The molecular basis of human keratin disorders

“…Just recently, another case of recessive BCIE has been described and a homozygous nonsense mutation in KRT10 was disclosed in close proximity to the previously described mutation (Tsubota et al 2008a). The heterozygous individuals are non-phenotypic carriers of the mutation indicating that one normal K10 allele is suYcient to maintain a normal KIF network.…”