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Advances in dermatology and venereology Acta Dermato-Venereologica
Striate Palmoplantar Keratoderma Showing Transgrediens in a Patient Harbouring Heterozygous Nonsense Mutations in Both DSG1 and SERPINB7
Ryo FUKAURA 1, 2, Takuya TAKEICHI 1, Yusuke OKUNO 3, 4, Daiei KOJIMA 4, Michihiro KONO 1, Kazumitsu SUGIURA 5, Yasushi SUGA 6 and Masashi AKIYAMA 1 * Departments of 1 Dermatology and 4 Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466- 8550, Japan, 2 UCL Medical School, University College London, UK, 3 Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, 5 Department of Dermatology, Fujita Health University School of Medicine, Toyoake, and 6 Department of Dermatology, Juntendo University Urayasu Hospital, Urayasu, Japan. * E-mail: makiyama @ med. nagoya-u. ac. jp Accepted Oct 26, 2016; Epub ahead of print Oct 27, 2016
Palmoplantar keratoderma( PPK) is a group of inherited skin disorders characterized by thickening of the skin on the palms and soles, often leading to pain. Classification has largely been clinical, but recently, causative genes for the various PPKs have been found, resulting in a need for a genetic classification of PPK( 1). The most common type in the Japanese population is Nagashima-type PPK( NPPK)( 2). This autosomal recessive condition is caused by a mutation in SERPINB7. The SERPINB7 protein is found in the stratum corneum of the skin, and its main function is to regulate intercellular protease activity( 3). The clinical features of NPPK include diffuse hyperkeratosis associated with erythema on the palms and soles and, in addition, on the dorsal aspects, known as transgrediens( 2). Another type of PPK, striate PPK( SPPK), is autosomal dominant. The clinical features include strips of hyperkeratosis running longitudinally along the hands and fingers, and generalized hyperkeratosis on the soles of the feet. A mutation in any of 3 genes is reported to be an underlying cause: desmoglein 1( DSG1), desmoplakin( DSP) and keratin 1( KRT1)( 4). Not only are these desmosomal proteins essential in maintaining the structure and integrity of the skin, but they are also essential to cell turnover( 5). DSP mutations have been shown to increase skin proliferation, leading to hyperkeratosis, and the same effect has been predicted with DSG1 mutations( 1), although the exact mechanism has not been fully clarified despite DSG1 being involved in various skin disorders( 6, 7). To date, there have been no reports of a patient with genetic mutations for 2 types of PPK. Here, we describe such a Japanese male.
CASE REPORT
A 36-year-old man presented with longstanding pain and hyperkeratotic palms. He had presented with corns on his palms in adolescence, which developed easily after sports. It was when he started working as a farmer that he noticed pain and“ stripe-like” hyperkeratosis on his palms, and circular areas of hyperkeratosis on the soles( Fig. 1A and B). He also had abnormalities on the dorsal aspects of the hands: poorly demarcated areas of erythema and maceration( Fig. 1C). No lesions were found on the dorsa of the feet. Although there were no white spongy changes after water immersion, as has been reported for some cases of NPPK, his palms were abnormally moist and malodorous compared with a healthy subject. The stripe-like pattern of hyperkeratosis on this patient’ s palms appeared to be a classical example of SPPK. However, the continuation of the lesions to the dorsal aspects, and a change in the lesions from hyperkeratosis to erythema were atypical. Instead, these seemed to resemble transgrediens reported in NPPK( 2). Other than a sister who has atopic dermatitis, he has no family history of hyperkeratosis or other skin disorders.
Fig. 1. Clinical and histological features of the patient.( A) Palms showing typical longitudinal hyperkeratotic lesions on the fingers.( B) Plantar aspects showing diffuse areas of hyperkeratosis.( C) Dorsal aspects of the hands, showing generalized erythema.( D) Pedigree of the family showing genotypes for the mutations in DSG1 and SERPINB7. wt: wild type, het: heterozygote.( E) Skin biopsy sample from the sole shows keratohyalin granules of various sizes, and acantholysis. Scale bar: 100 µ m.( F) Electron microscopy clearly shows a highly electron-dense line. Magnification: × 20,000.
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 / 00015555-2553 Acta Derm Venereol 2017; 97: 399 – 401