LAUSR

Dear Editor, Mal de Meleda (MDM, OMIM 248300) is a rare autosomal recessive (AR) palmoplantar keratoderma (PPK) with an estimated prevalence of 1 in 100,000 and was first reported on the Croatian island of Meleda (now Mljet) by Luca Stulli in 1826. MDM is caused by biallelic mutations in the SLURP-1 gene (locus 8q24.3), which encodes the secreted mammalian Ly-6/ urokinase-type plasminogen activator receptor (uPAR)-related protein-1(SLURP-1). Clinically, the onset of MDM is typically soon after birth and characterized by a transgredient (plantar surface progressing to dorsal surface) and progredient (worsening with age) pattern of hyperkeratosis of the palms and soles. Here, we give a report in Chinese Mainland with respect to a family definitely diagnosed with MDM with the homozygous mutation c.256G>A (p.G86R) and presenting higher phenotypic variability. A 25-year-old Chinese man presented with sharply demarcated hyperkeratotic plaques on the palms and soles from birth, which extended to the dorsum of the hands and feet with age. An additional complication for him included palmoplantar hyperhidrosis. On cutaneous examination, we observed sharply demarcated hyperkeratosis of palms and soles (Fig. 1a,b), which extended to the dorsum of the hands and feet in a “glove-and-socks” distribution (Fig. 1c). Erythema and hyperkeratosis extended to the wrists, ankles, and achilles tendon area. Nail changes were observed including thickening and hypercurvature. The elbows, knees, and perianal skin were spared. No evidence of epithelial malignancies, such as malignant melanoma, was found. His parents were clinically unaffected, and no consanguineous relationship was found in his family. Acitretin was prescribed to the patient, but he failed to adhere to medication for personal reasons. DNA samples from the patient, his parents, and 100 unrelated healthy individuals were screened for SLURP-1 gene mutation. Homozygous missense mutation c.256G>A (p.G86R) in exon 3 of SLURP-1 gene was found in the patient. His parents were all heterozygous carriers. These nucleotide substitutions were not found in 100 unrelated control individuals (Fig. 2a–d). To date, 20 pathogenic mutations of the SLURP-1 gene have been described in the literature. The c.256G>A (p.G86R) variation is a recurrent mutation most often found in Asian origin. Homozygous missense mutation c.256G>A (p.G86R) in SLURP-1 has been previously reported in patients from Palestine, Pakistan, Indonesia, Taiwan, and the Chinese Mainland. The affected residue Gly-86 is in loop 3 at a site (a) Lesions on palms