SHORT REPORT A novel heterozygous nonsense mutation of keratin 5 in a chinese family with Dowling–Degos disease L. Guo, †,‡ X. Luo, § A. Zhao, †,‡ H. Huang, § Z. Wei, †,‡ L. Chen, § S. Qin, – L. Shao, – J. Xuan, – G. Feng, – C. Minghua, § J. Luan, § L. He, †,‡,–, * Q. Xing †,‡, * † Children’s Hospital, Fudan University, Shanghai, China ‡ Institutes of Biomedical Sciences, Fudan University, Shanghai, China § Huashan Hospital, Fudan University, Shanghai, China – Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Center, Shanghai Jiao Tong University, Shanghai, China *Correspondence: L. He; Q. Xing. E-mail: helinhelin@gmail.com; xingqinghe@hotmail.com Abstract Background Dowling–Degos disease (DDD; MIM 179850) is an autosomal dominant genodermatosis caused by mutations in keratin 5 gene (KRT5). KRT5 is specifically expressed in basal layer of epidermis and plays an important role in protecting epithelial cells from mechanical and non-mechanical stresses. Objective We analysed the molecular basis of DDD in a Chinese family. Methods Genomic DNA of the Chinese DDD family and a matched control cohort was isolated according to standard techniques. All exons of the KRT5 gene and adjacent exon–intron border sequences were amplified using PCR and directly sequenced. Results We identified a novel keratin 5 (K5) nonsense mutation designated c.C10T (p.Gln4X) in exon 1 of the KRT5 gene. Conclusion Our data expand the spectrum of mutations in the KRT5 gene underlying DDD. Received: 16 November 2010; Accepted: 20 April 2011 Conflicts of interest None declared. Dowling–Degos disease (DDD; MIM 179850) is a rare autosomal dominant genodermatosis characterized by reticulate pigmentation mainly affecting flexures, such as the neck, axilla and areas below the breasts and groin 1,2 . Additional reported features include com- edo-like lesions on the neck, perianal and genital reticulated pig- mented lesions 3 and pitted perioral acneiform scars. 4 In 2006, Betz et al. localized the locus for DDD to a region containing the type II keratin gene cluster and found a loss-of-expression mutation in the keratin 5 gene (KRT5). 5 A couple of novel null-mutations were also found in exon 1 of KRT5 in European case. 5–7 In this study, we identified a novel keratin 5 (K5) nonsense mutation in an extended Chinese family with DDD. A family with autosomal dominant DDD was recruited from the Fujian province of China (Fig. 1). The proband (III:1) was a 56-year-old male patient, who had experienced abdominal hyper- pigmented and hypopigmented macules since the age of 19. With age mottled pigmentation gradually extending to his face and upper limbs, blisters and pruritus accompanied by worsened pig- mentation sometimes occurred after exposure to sunlight or in a high temperature environment. A skin rash appeared, mainly on the head, face, neck, trunk and upper limbs. Sporadic and wide- spread hyperpigmented spots and plaques were observed on the face and the side of the neck accompanied by mild telangiectasia (Fig. 2a). Moist red-brown hyperkeratotic plaques were found both in the inguen area and in armpits (Fig. 2b). Hypopigmented spots were found at the abdomen and at the lower back (Fig. 2c). Inflammatory papules, papulovesicles and scratch scabs were also in evidence at the anterior area of the neck. Milky white flat papules, 10-mm in diameter, were observed at the anterior area of the neck of individual IV:1 (Fig. 2d). A biopsy taken from the lower back demonstrated digitated elongations of the hyperpig- mented rete ridges (Fig. 2e). Another biopsy of the neck revealed branching and pigmented downward proliferations of the epider- mal cells with numerous melanin-laden melanophages having infiltrated the papillary dermis (Fig. 2f). The histological findings in the lesion from the axillae showed similar extensive changes, although the pigmentation of rete ridges was absent (Fig. 2g). On The first two authors contributed equally to this work. ª 2011 The Authors JEADV 2011 Journal of the European Academy of Dermatology and Venereology ª 2011 European Academy of Dermatology and Venereology DOI: 10.1111/j.1468-3083.2011.04115.x JEADV