Shinichi Yotsumoto

Novel mutations in GJB2 encoding connexin‐26 in Japanese patients with keratitis–ichthyosis–deafness syndrome

Summary Background Germline missense mutations in the GJB2 gene that encodes connexin‐26 (Cx26) have recently been found to be the cause of the keratitis–ichthyosis–deafness (KID) syndrome.

A new case of alpha-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Meniere's syndrome and without mental retardation

α‐N‐acetylgalactosaminidase (α‐NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three α‐NAGA‐deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described. We report a further case in a 47‐year‐old Japanese woman, the product of a consanguineous marriage. The remarkable findings in this patient were her normal intelligence, Ménières syndrome, disturbance of peripheral sensory nerves, hearing loss and cardiac hypertrophy. α‐NAGA enzyme activity in her plasma was 0·77% of the normal value. Other enzyme activities, such as α‐galactosidase, β‐galactosidase, α‐l‐fucosidase, β‐mannosidase and aspartylglucosaminidase, were within normal limits. A large quantity of amino acid O‐glycans was detected in her urine. Gene analysis revealed a novel point mutation (G→A transition) at nucleotide 11018 (986 in the cDNA) resulting in an Arg‐329‐Gln substitution. Kanzaki disease has the same enzyme defect as Schindler disease, but the manifestations are quite different.

Morphological and biochemical studies of human beta-mannosidosis: identification of a novel beta-mannosidase gene mutation.

Summary Background There are seven well‐known lysosomal storage diseases that produce angiokeratoma corporis diffusum clinically. β‐Mannosidosis (MANB1; OMIM248510), first reported in humans in 1986, is a rare hereditary lysosomal storage disease caused by a deficiency of the enzyme β‐mannosidase. Since then, 13 cases of β‐mannosidase deficiency in ten families have been described. A human β‐mannosidase mutation has been reported only by Alkhayat et al. in 1998.

Selenium deficiency: report of a case

We report an 18‐month‐old Japanese boy with selenium deficiency. He had dry skin with irregularly shaped, erythematous changes on the cheeks, groin, hip, and extremities, erosions on the external urethral and anal orifices, and sparse, short, thin, light‐coloured hair. He had received parenteral nutrition for 5 months because of juvenile polyposis. At presentation, his serum selenium level was less than 2.0 µg/dL (normal range, 10.6–17.4 µg/dL). His skin lesions responded well to supplementary treatment with sodium selenite. His skin symptoms were similar to those attributable to a deficiency of zinc which, like selenium, is an essential trace element. According to the literature, selenium deficiency is responsible for cardiomyopathy, which was diagnosed in our patient. The clinical similarity to zinc deficiency and the literature yielded important clues for a diagnosis of selenium deficiency in this patient.

Estrogen Dermatitis: A Dendritic-Cell-Mediated Allergic Condition

Background: Most estrogen dermatitides are induced by local or systemic contact dermatitis where dendritic cells are central, and tamoxifen has a blocking effect on dendritic cells. Methods: We present 5 cases of estrogen dermatitis in which the clinical features were prurigo, urticaria, acneiform eruption and annular erythema. Results: Tamoxifen was effective in 3 of 4 cases. Three of 4 biopsy specimens showed the formation of Langerhans cell nests in the epidermis and hair follicles and perivascular infiltration of CD4+ and CD8+ lymphocytes in the dermis. Conclusion: These results suggest that a dendritic-cell-mediated allergic mechanism is involved in estrogen dermatitis.

A case of follicular mucinosis treated successfully with minocycline.

q 2000 British Association of Dermatologists, British Journal of Dermatology, 142, 812±851 For general consideration regarding the ecology and taxonomy of Alternaria spp. the reader is referred to Acland et al. A. tenuissima, together with A. alternata and A. chartarum, are the species most involved in human pathology, but other rarer Alternaria spp. have also been reported. Factors such as immunosuppression, local wounds or systemic disease are generally present, but cases without predisposing factors are described, and are probably due to factors inherent to the fungus. Formerly said to be rare, cutaneous alternariosis could be more frequent than thought, and we suspect that it is under-diagnosed. This might be due to either extreme variability and non-specificity of the appearance of infected skin, or to insufficient use of mycological investigations. Alternatively, it may be apparently under-reported simply because many case reports are spread in a myriad of either low-impact or vernacular journals of various ages. Treatment of cutaneous Alternaria infections is not standardized, and lack of consensus will probably persist, owing to the fact that such cases are relatively infrequent and multicentre case±control studies are not easily feasible. However, these patients, who often are in a critical condition, have to be treated immediately. Following examples of treatment of systemic dematiaceous fungal infections with terbinafine, we propose the use of this well-tolerated and rapid-acting drug in cutaneous alternariosis.

Histopathologic and Ultrastructural Studies of Angiokeratoma Corporis Diffusum in Kanzaki Disease

A novel metabolic disease, angiokeratoma corporis diffusum (Kanzaki), was the subject of an extensive histopathologic and ultrastructural study. Findings included dilated lymph and blood vessels in the upper dermis with an orthokeratortic, thickened, horny layer in well developed angiokeratoma. In the early papules, a few sporadic dyskeratotic keratinocytes were present in the epidermis with or without a thickened horny layer. Vesicular clear vacuolation was clearly observed in the cytoplasm of the secretory portion of the eccrine sweat glands, but none was observed in the vascular endothelial cells with hematoxylin‐eosin staining. Using electron microscopy, lysosomal vacuolation was observed in many cell types, including eccrine sweat gland cells, vascular endothelial cells, dermal fibroblasts, dermal neural cells, lymphocytes of peripheral blood in the skin, and glomerular endothelial cells, but none was noted in the epithelial cells of the kidney. Widely dilated vacuoles were found to contain only a small amount of fuzzy filamentous material in the vascular endothelial cells, filamentous or electron‐dense granular substances in fibroblasts, and electron‐dense, lamellated or homogeneous structures in eccrine sweat gland cells and in neural cells. Ultracytochemical examination revealed glycoconjugates in dilated lysosomes. Characteristics of Kanzaki Disease were shown to differ from those of Fabry disease or any other lysosomal storage disease.

Mutations in the ED1 gene in Japanese families with X-linked hypohidrotic ectodermal dysplasia

Abstract: X‐linked hypohidrotic ectodermal dysplasia (XLHED; OMIM 305100) is characterized by sparse hair, abnormal teeth and decreased sweating as a result of abnormal development of the sweat glands. Mutations in the ED1 gene, which encodes ectodysplasin‐A (EDA), are responsible for XLHED. Ectodysplasin‐A, a ligand for the EDA receptor, plays an important role in epidermal morphogenesis. We identified ED1 mutations including three novel mutations by sequencing genomic DNAs from eight unrelated Japanese XLHED families. Data from all reported mutations revealed that codon 156 in the furin subdomain is the most frequent site of change in EDA.

Analyses of the transglutaminase 1 gene mutation and ultrastructural characteristics in a Japanese patient with lamellar ichthyosis

We described a Japanese female with lamellar ichthyosis whose transglutaminase 1 gene (TGM1 gene) was mutated. DNA sequence analysis revealed that the patient had a homozygous mutation, i.e. a point mutation from G to A at nucleotide 1494 resulting in the substitution of glycine for arginine at codon 143. Her mother was heterozygous for this mutation. In situ transglutaminase assay in the patients skin showed loss of enzyme activity. Ultrastructural examination revealed incomplete formation of cornified cell envelopes and electron-dense materials adjacent to plasma membranes. These results suggest that defective transglutaminase activity caused by homozygous TGM1 gene mutation (G143R) results in disruption of cornified envelope assembly and the clinical phenotype of lamellar ichthyosis.

A Case of Chromomycosis with Tumor-like Growth

A 66‐year‐old man who lived on Tokunoshima Island, a small and remote southern island of the Japanese archipelago, had suffered from chromomycosis for more than 30 years and presented with a tumor‐like growth on the posterior crural region of his right leg. Fonsecaea pedrosoi was identified as the pathogen from its growth pattern and micromorphological characteristics. The patient was successfully treated with 5‐fluorocytosine, itoraconazole, and topical thermotherapy.