Epidermolytic palmoplantar keratoderma (EPPK; MIM 144200) is an autosomal dominant inherited genodermatosis characterized by diffuse thickening of the epidermis over the palms and soles. 1 Histopathologically, EPPK presents characteristic features of epidermolytic hyperkeratosis, perinuclear vacuolation and cytolysis of the suprabasal keratinocytes. A transmission electron microscopy study of the epidermolytic hyperkeratosis has revealed an abnormal keratin intermediate filament network and tonofilament clumping. 2 Similar features have been observed in various keratin diseases, such as bullous congenital ichthyosiform erythroderma (BCIE) and ichthyosis bullosa of Siemens (IBS) caused by mutations in keratin 1/10 and 2e, respectively. 1 Consequently, the candidate gene for mutations in EPPK was also considered to be a keratin-related gene. This suggestion was subsequently supported by linkage analysis, which mapped EPPK to KRT9, encoding keratin 9, a type I keratin that is expressed tissue specifically in the suprabasal keratinocytes of the palmoplantar epidermis. 3 Subsequently, KRT9 mutations have been demonstrated in patients with EPPK. All KRT9 mutations recorded so far have occurred in the 1A or 2B rod domain of keratin 9, although only a single mutation has been recorded in the 2B rod domain. 1,4,5 In this study, we examined a Japanese family with EPPK. We present the first report of a missense KRT9 mutation within the 2B rod domain of keratin 9. Ó 2006 British Association of Dermatologists • British Journal of Dermatology 2006 155, pp624-626 L457F mutation in the 2B rod domain of keratin 9, A. Kon et al. 625 importance of the leucine residue in the corresponding locations of various kinds of keratin polypeptides for maintenance of the keratin intermediate filament network.

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A 7BeCl2 solution containing 0.5 micrograms Be per mouse was injected subcutaneously, intraperitoneally, intramuscularly, intrathoracically, and intravenously, and distribution was observed for periods up to 1 wk. 7Be was excreted more rapidly following intravenous injection than by the other routes of injection. The amount of Be found in the liver or the spleen was substantial at 1 d after intraperitoneal injection. It increased more in the spleen at 7 d after either intraperitoneal or intrathoracic injection. On the other hand, the amounts of Be stayed almost constant in the kidneys, by the various routes of injection. When injected intrathoracically, the amounts of Be in the heart and the lung were greater than when administered by the other routes of injection. The amounts of Be in the femurs of mice administered by these routes of injection, except with intravenous injection, were greater than in the other organs. The percentage of 7Be in the mineralized bone was 90% of that of 7Be in the femurs when injected intraperitoneally or intrathoracically. However, the ratio of Be in the mineralized bone to that in the bone marrow was 3 to 2. Beryllium had thus a closer affinity for the femurs than for the other organs investigated, with the different modes of administration used. The amount of Be in the entire skeleton was estimated to be substantial. Within the limitations of 1 wk of exposure, the skeleton would appear to be a critical organ. This would suggest that osteosarcomas may occur following administration of Be to laboratory animals for a long-term period.

Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease caused by a decreased activity of hydroxymethylbilane synthase (HMBS). Regarding the abnormalities of the HMBS gene, many different mutations have been reported worldwide; however, few families from Japan have been studied. In this work, we investigated the presence of mutations in two unrelated Japanese patients with AIP. Mutational analysis was performed using the polymerase chain reaction-single strand conformation polymorphism (SSCP) method, followed by DNA sequencing. Reliable restriction enzyme cleavage assays were also established for the pedigree analyses. Unique SSCP patterns were noted in exons 12 and 15 of the HMBS gene. Sequencing revealed different mutations in each patient: a two-base deletion of CT at nucleotide 730-731 (730delCT), and also a two-base deletion of CA at position 982-983 (982delCA). Both of the deletion mutations lead to truncated proteins with an abnormal C-terminus, which would be expected to decrease the stability and/or activity of HMBS. Using the cleavage assays, we were able to definitively identify gene carriers in the family. This study adds a novel mutation to those that have been previously reported, and emphasizes that molecular analysis would be very useful not only for the identification of asymptomatic gene carriers in the family but also for the detection of ancestral founders in porphyria families.

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