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ActaDV ActaDV
Advances in dermatology and venereology Acta Dermato-Venereologica
Extensive Post-zygotic Mosaicism of KRT1 or KRT10 Mutation Mimicking Classical Epider molytic Ichthyosis
Maella SEVERINO-FREIRE 1, Nathalie JONCA 2, Melanie PICHERY 2, Emilie TOURNIER 3, Nicolas CHASSAING 2, 4 and Juliette
MAZEREEUW-HAUTIER 1, 2 1
Department of Dermatology, Toulouse University Hospital, Toulouse, 24 chemin de Pouvourville TSA 30030, FR-31059 Toulouse cedex 9, 2 U 1056 INSERM, FRE 3742 CNRS, Université Toulouse III‘ Différenciation Epithéliale et Autoimmunité Rhumatoïde’ Place du Dr Baylac,
3
Anatomo Pathology Department, IUC Oncopole, and 4 Medical Genetics Department, CHU Purpan, Paul Sabatier University, Toulouse, France. E-mail: maella. severino @ hotmail. fr Accepted Oct 6, 2016; Epub ahead of print Oct 10, 2016
Epidermolytic ichthyosis( EI) is a rare disorder of keratinization belonging to the group of keratinopathic ichthyosis. EI is an autosomal dominant disease due to mutations in the genes encoding keratin 1( KRT1) or keratin 10( KRT10) expressed in the suprabasal layers of the epidermis( 1). EI is characterized by erythroderma, blistering and erosions at birth, followed by generalized hyperkeratotic and verrucous lesions from early childhood. The lesions are generalized and palmo-plantar keratoderma may be seen( 2). EI is a severe disease due to skin aspect, itching and recurrent episodes of skin infections with malodorous skin. Histological examination of skin lesions shows thickening of the stratum corneum, vacuolar degeneration of the epidermal suprabasal layer, and some clumping of tonofilaments in the keratin. Whereas EI is in the form of generalized skin lesions, localized segmental lesions along the Blaschko’ s lines have been reported rarely as a consequence of post-zygotic somatic mutations in KRT1 or KRT10. Post-zygotic mosaicism in EI must be distinguished from epidermolytic naevi, a naevoid variant of keratinopathic ichthyosis characterized by localized hyperkeratotic lesions present at birth without an initial phase of blistering( 3, 4). Post-zygotic mosaicism in EI usually has a limited distribution. We report here 2 cases of EI with an extensive distribution.
CASE REPORT
Two patients( 1 male, 1 female, aged 30 and 17 years, respectively), with unaffected parents, presented at birth with blisters, erosions and erythroderma. They developed extensive, but not generalized, hyperkeratotic lesions distributed along the lines of Blaschko, involving 40 % and 80 % of body surface area, respectively. The male patient had skin lesions located on the folds, as well as on the trunk, limbs, palms and soles( Fig. 1a – c). The female patient had extensive verrucous plaques, which were more pronounced in the folds and back( Fig. 1d – f). She had no palmo-plantar involvement. Histopathological examination of her lesional skin showed major epidermolytic hyperkeratosis, sometimes with parakeratotic and degenerative lesions in the granular layer.
Sequencing of KRT1 and KRT10 genes was performed by the Sanger method. For the male patient, molecular analysis of lesional skin revealed the heterozygous mutation c. 526 _ 531delGTGAAG in exon 1 of KRT1. This mutation predicted a deletion of 2 amino acids in the encoded protein( p. Val176 _ Lys177del). It was also detected in leukocytes from peripheral blood, but the sequence
Fig. 1. Male patient:( a) Hyperkeratotic lesions distributed along the lines of Blaschko in the elbow fold and forearm.( b, c) Severe hyperkeratosis of the palms and foot. Female patient:( d, f) Hyperkeratotic lesions distributed along the lines of Blaschko in the elbow and knee folds.( e) More pronounced hyperkeratotic verrucous plaques located in the back and folds.
corresponding to the mutant allele was in a lower proportion compared with the normal sequence( Fig. S1a 1). For the female patient, the mutation c. 466C > T( p. Arg156Cys) in exon 1 of KRT10 was identified from peripheral blood leukocytes as well as from saliva. In both tissues, electropherograms showed that the mutated allele was in a lower proportion compared with the wild-type allele( we estimated that two-thirds of the cells carried this mutation). This was subsequently confirmed by next-generation sequencing using a targeted panel involved in ichthyosis( Fig. S1b 1). Among the 226 reads of the region, 84( 37.2 %) were found to bear the mutation.
1 https:// www. medicaljournals. se / acta / content / abstract / 10.2340 / 00015555-2542
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2542 Acta Derm Venereol 2017; 97: 387 – 388