No abstract

Pachyonychia congenita type 2 (PC-2; MIM#167210), also known as Jackson-Lawler type (Jackson and Lawler, 1951), is a rare autosomal dominantly inherited disease characterized by hypertrophic nail dystrophy, focal keratoderma, multiple pilosebaceous cysts, natal teeth, and hair abnormalities (McKusick, 2001). Heterozygous missense mutations of the keratin 17 (K17) gene have been identi®ed in PC-2 (McLean et al, 1995). A mutation in the keratin 6b gene, which encodes K6b, the expression partner of K17, has also been reported in PC-2 (Smith et al, 1998). By sequencing genomic DNA from our PC-2 patient, we found a novel heterozygous mutation (G®A transition at nucleotide 452, 452G>A) in the helix initiation motif of the K17 gene resulting in a predicted substitution of valine (GTG) for methionine (ATG) at codon 102, V102M.A 19-y-old Japanese man visited our university clinic in March 2000. All of his nails had become thick 2 mo after birth. He had multiple normally colored papules and cysts on his scalp and axilla since he was 5 y old, and had hyperkeratosis with blister formation on his soles since he was 10 y old. At 16, the cysts on his scalp and axilla became painful and were repeatedly infected. His father, mother, and younger brother are healthy.Physical examination showed that he had many cysts and nodules all over his body, pachyonychia on all his ®ngers and toes, pili torti (twisted hair), and plantar hyperkeratosis with bullae. His eyebrows stand erect (Fig 1A). His mouth, tongue, and teeth were normal. Histologic examination of a subcutaneous cyst showed that the cyst wall was composed of several layers of epithelial cells accompanied by sebaceous gland lobules. Therefore, a diagnosis of steatocystoma was made.After informed consent, genomic DNA was extracted from a sample of his peripheral blood lymphocytes by a standard method (Qiagen, Hilden, Germany). Genomic DNA from 50 normal healthy Japanese people was used as a control. Exon 1 of the K17 gene was ampli®ed by polymerase chain reaction (PCR) with speci®c primers for the K17 gene as described previously (McLean et al, 1995). Nested PCR was initially performed using primers K17p8 (5¢-GCC TAT AAA GGA AGC GGG C-3¢) and K17p10 (5¢-CTC CTT TCT GCC TCC TCC T-3¢) and then primers K17p3 (5¢-TAT GGC AGC AGC TTT GGG-3¢) and K17p4 (5¢-GGT ACC AGT CAC GGA TCT TCA-3¢). Ampli®cation conditions were 95°C for 1 min, followed by 35 cycles of 95°C for 40 s, 58°C for 40 s, and 72°C for 1 min, and a ®nal extension at 72°C for 3 min. PCR products (157 bp) were puri®ed using a QIA quick PCR puri®cation kit (Qiagen), and were sequenced on an Applied Biosystem 310 automated sequencer using an ABI PRISM ¯uorescent dye terminator system (Perkin Elmer, Foster City, CA).Direct sequencing of DNA from the patient revealed a point mutation, 452G>A. This transition results in the substitution of a valine for a methionine (V102M). Another sequence change was found (T®C transition at nucleotide 457, 457T>C) but this transition does not change the predicted amino acid. To con®rm whethe...

Darier disease (DD; MIM 124200) is an autosomal dominant disorder that usually presents in teenagers or adults with multiple keratotic papules or plaques in seborrhoeic areas, although considerable clinical diversity may exist. 1 Nevertheless, skin biopsy typically shows suprabasal acantholysis of the epidermis with overlying dyskeratotic cells, and transmission electron microscopy reveals loss of desmosomal attachments and perinuclear aggregates of keratin intermediate filaments. 2 Moreover, all cases of DD, whatever the nature of the clinicopathological manifestations, appear to be due to heterozygous mutations in the ATP2A2 gene. 3,4 One unusual clinical presentation is the acral haemorrhagic variant, haemorrhagic DD (HDD), 5 which has been rarely reported. [6][7][8] In this report, we describe a Japanese family with HDD. This pedigree is of interest because of the difficulties in making a clinical diagnosis and also the nature of the underlying ATP2A2 mutation which has implications for genotype-phenotype correlation in this genodermatosis.

We report a 71-year-old woman with antiepiligrin cicatricial pemphigoid associated with nephrotic syndrome. She presented with a six-month history of pruritic blisters over her trunk and legs. She also had episodes of recurrent painful oral erosions. A skin biopsy showed a subepidermal bulla, and a direct immunofluorescence (DIF) study revealed linear deposition of IgG and C3 at the basement membrane zone (BMZ). Indirect immunofluorescence (IIF) staining of 1 M NaCl-split skin demonstrated circulating IgG autoantibodies reactive with the dermal side. Immunoprecipitation studies of the patient's serum disclosed IgG autoantibodies directed against a set of polypeptides that corresponded to laminin 5 (beta 3 gamma 2). Based upon the long-standing edema of her legs and her hypoproteinemia, she was diagnosed with nephrotic syndrome. To our knowledge, the association of antiepiligrin cicatricial pemphigoid with nephrotic syndrome has not been reported previously.

Patent blue is a dye that has been used for intraoperative lymphatic mapping. We used this mapping method on a patient with lymphorrhea after groin dissection. We easily detected the lymphatic channel causing lymphorrhea and successfully ligated it. This technique may have great merit for treating of lymphorrhea.