SIR, Striate palmoplantar keratoderma (SPPK; OMIM 148700) is a rare, mainly autosomal dominant, genodermatosis characterized by linear hyperkeratosis of the volar aspects of the fingers, extending onto the palm. 1 There is strong evidence that SPPK is caused by defects in desmosomes, the major epithelial intercellular adhesion junctions, which confer strength and rigidity to tissues that experience high mechanical stress. Causative mutations in genes encoding the desmosomal proteins desmoglein 1 (Dsg1) and desmoplakin (DP), and keratin 1 which links to desmosomes, have been reported in 20 cases. 2–7 We report a novel mutation in the DSG1 gene in a threegeneration kindred in which four members were affected with SPPK.

The proband (II-1) was a 40-year-old Scottish man (Fig. 1a). He presented with painful thickening of the skin on his palms (Fig. 1b) and soles, hyperhidrosis and intermittent associated blistering, since childhood. Clinical examination showed linear hyperkeratosis of the volar aspect of fingers, more extensive focal plantar hyperkeratosis and mild hyperkeratosis of the knees. His father, paternal uncle and 8-year-old daughter were similarly affected. Following informed consent, a biopsy of affected medial plantar skin was obtained from the proband and processed for light and electron microscopy by standard methods, 8 and skin was also snap frozen in liquid nitrogen for immunohistochemistry. Genomic DNA was extracted from saliva samples taken from the proband, his affected daughter and his unaffected son (II-1, III-1 and III-2). Based on previous studies implicating genetic mutations of desmosomal proteins in PPK, 3, 4, 9 we carried out mutational analysis of the DSG1 gene. Polymerase chain reaction (PCR) amplification of each exon of DSG1, including exon⁄ intron boundaries was performed using primers previously described3 on both affected patients and the unaffected son and compared with a normal control. PCR products were sequenced on an ABI 3130 or 3730 automated sequencing machine (Applied Biosystems, Foster City, CA, USA), as per standard protocols. 10 Light microscopy of affected plantar epidermis showed acanthosis with mild spongiosis and intracellular vacuolation. The granular layer was thickened and hyperkeratosis was present. A mild upper dermal perivascular chronic inflammatory cell infiltrate and suprabasal cell–cell separation was noted. Electron microscopy revealed normal keratin intermediate filaments but separation of keratinocytes in the spinous layer. Immunohistochemistry showed prominent staining of Dsg1 in the suprabasal, spinous and lower granular layers.