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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