Acta Dermato-Venereologica 99-4CompleteContent | Page 27

458 SHORT COMMUNICATION A Japanese Case of Galli–Galli Disease due to a Previously Unreported POGLUT1 Mutation Michihiro KONO 1 , Masaki SAWADA 2 , Yuka NAKAZAWA 3,4 , Tomoo OGI 3,4 , Yoshinao MURO 1 and Masashi AKIYAMA 1 Departments of 1 Dermatology and 3 Human Genetics and Molecular Biology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, 2 Division of Dermatology, Japanese Red Cross Nagoya Daiichi Hospital, and 4 Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. E-mail: [email protected] Accepted Jan 16, 2019; E-published Jan 17, 2019 Galli–Galli disease (GGD) is a rare autosomal dominant genodermatosis exhibiting reticulated hyperpigmentation and scaling erythematous papules mainly on the great skin folds (1). GGD is considered to be an acan­tholytic variant of Dowling–Degos disease (DDD) (2). Mutations in KRT5 (3) and POGLUT1 (4) have been reported in GGD patients. In contrast, DDD is a rare autosomal dominant genetic pigmen- tary disorder characterized by dot-like or reticulate, slightly depressed, sharply demarcated brown macules particularly affecting the flexures and other major skin folds. KRT5 was identified as a causative gene of DDD in 2006 (5), and recently POFUT1 (6) and POGLUT1 (4) were clarified as additional causative genes. Finally, PSENEN was identified as a causative gene of DDD with hidradenitis suppurativa (7). Here, we report a Japanese female GGD case with a previously unreported POGLUT1 mutation. As far as we know, the present case is the first non-Caucasian GGD patient with a POGLUT1 mutation. CASE REPORT A 50-year-old Japanese woman had noticed small pigmented spots on the extremities in her late twenties that had increased in number gradually. According to her, her mother had similar pigmented macules. Neither of her daughters (ages 20 years and 16 years) had similar pigmented macules. She visited our neighbor hospital and was referred to our department for diagnosis of the hyperpigmented macules mainly on the extremities (Fig. 1A). She showed irregularly shaped, slightly keratotic, sharply de- marcated grayish-brown macules of 2 to 5 mm in diameter on the extremities and the trunk. The lesions were more sparse on the trunk than on the extremities. Neither a reticulate arrangement of the macules nor depression of the macules was observed in the present patient. The macules on the extremities were mainly seen on the dorsal side. The number of macules on the extremities gradually increased from the proximal to the distal regions. The flexor sides of the knees and elbows and other major skin folds were spared (Fig. 1B). A few erythematous lesions with itching were intermingled with the brown macules. Palmoplantar pits and pigmentation were absent. She showed fewer macules on the face and the V-neck site, and the neck was completely spared (Fig. 1D). Faint depigmented macules were also seen on the extremities and at the V-neck site. A skin biopsy obtained from a pigmented macule on the forearm showed elongation of the rete ridges with diffuse pigmentation in the epidermis and hyperkeratosis without parakeratosis. Under high magnification, acantholysis and atypism of keratinocytes were seen in the epidermis. The lesional epidermis was thinner than that of the surrounding normal skin (Fig. 1G). Patchy inflammatory cell infiltration and pigmentary incontinence were seen in the upper dermis (Fig. 1E, F). From the above information, the differential diagnoses were GGD, which is an acantholytic variant of DDD, and xeroderma pigmentosum (XP), variant type. We confirmed our diagnosis by genetic analysis. doi: 10.2340/00015555-3119 Acta Derm Venereol 2019; 99: 458–459 Fig. 1. The clinical and histopathological features of the patient. (A) The pedigree of the proband’s family. (B-F) Skin manifestations of the proband. The macules on the extremities are mainly on the dorsal side. The number of macules on the extremities gradually increases from the proximal to the distal regions (B). Irregularly shaped, slightly keratotic, sharply demarcated grayish-brown macules of 2 to 5 mm in diameter are seen on the dorsal hands (C). Only a small number of macules are seen at the V-neck site. Faint depigmented macules are seen at the V-neck site (D). (E–G) Histopathologically, elongation of the rete ridges with diffuse pigmentation is observed in the epidermis and patchy inflammatory cell infiltration is seen in the superficial dermis (E). Under high magnification, acantholysis and atypism of epidermal keratinocytes are seen and pigmentary incontinence is observed in the upper dermis (F). The lesional epidermis (right side) is thinner than that in the adjacent normal skin (left side), and hyperkeratosis without parakeratosis is seen in the stratum corneum (dotted line, a border of the lesion) (G). The Ethics Committee of the Nagoya University Graduate School of Medicine approved the studies described below. All studies were conducted according to the principles of the Declara- tion of Helsinki. The participant gave written informed consent. Whole-exome sequencing was performed with genomic DNA from the patient’s peripheral blood sample. We found a heterozy- gous frameshift mutation, c.1013delTinsAAC, p.Ile338Lysfs*27, This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.