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The high percentage of patients with the same TGM1 mutations, together with the high number of homozygous probands (64%), indicates the existence of a strong founder effect in our population.

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The skin has the necessary elements to respond to growth hormone (GH) and suffers clinical changes in the pathological circumstances of excess and deficiency of GH. The GH has been involved in the development of different types of human neoplasms. Based on these data, we have studied the GH receptor (GHR) expression in acrochordons, seborrheic keratosis, melanocytic nevi, histiocytomas, squamous cell carcinomas, basal cell carcinomas, and malignant melanomas by means of the immunohistochemistry with the monoclonal antibody MAb 263. All the entities showed immunoreactivity for GHR. In the histiocytomas, the expression of GHR in the keratinocytes of the hyperplastic epidermis coating the lesion showed a strong nuclear pattern, but the non-hyperplastic epidermis of the edges of the histiocytomas expressed GHR with a cytoplasmic pattern. In the basal cell carcinoma and squamous cell carcinoma, the immunoreactivity was weaker than in normal skin. In the squamous cell carcinoma, the intensity of immunostaining correlated directly with the grade of cellular differentiation. In conclusion, the GH may be involved in the development of different kinds of cutaneous neoplasms, and the intracellular localization of GHR may imply a functional significance, at least in the histiocytomas.

Confluent and reticulated papillomatosis (CRP) is a rare dermatosis of unknown aetiology whose relationship to Malassezia furfur is still debated. Antifungal agents, antibiotics, retinoids, and, more recently, calcipotriol have been successfully used as treatment. The authors report on a 14-year-old female with confluent and reticulated papillomatosis in whom M. furfur was found. Anti-fungal therapy eliminated the fungus, but did not achieve the disappearance of the lesions. Further treatment with tacalcitol was successful, supporting the theory that CRP might be a disorder of keratinization. To the authors' knowledge, this is the first patient treated with tacalcitol for this entity.

BackgroundMutations in the TGM1 gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ∼46%, ∼21% and ∼13% of all TGM1 gene mutations, respectively. Moreover, these mutations were reported only once outside of Galicia, pointing to the existence of historical episodes of local severe genetic drift in this region.Methodology/Principal FindingsIn order to determine whether these mutations were inherited from a common ancestor in the Galician population, and to estimate the number of generations since their initial appearance, we carried out a haplotype-based analysis by way of genotyping 21 SNPs within and flanking the TGM1 gene and 10 flanking polymorphic microsatellite markers spanning a region of 12 Mb. Two linkage disequilibrium based methods were used to estimate the time to the most recent common ancestor (TMRCA), while a Bayesian-based procedure was used to estimate the age of the two mutations. Haplotype reconstruction from unphased genotypes of all members of the affected pedigrees indicated that all carriers for each of the two mutations harbored the same haplotypes, indicating common ancestry.Conclusions/SignificanceIn good agreement with the documentation record and the census, both mutations arose between 2,800–2,900 years ago (y.a.), but their TMRCA was in the range 600–1,290 y.a., pointing to the existence of historical bottlenecks in the region followed by population growth. This demographic scenario finds further support on a Bayesian Coalescent Analysis based on TGM1 haplotypes that allowed estimating the occurrence of a dramatic reduction of effective population size around 900–4,500 y.a. (95% highest posterior density) followed by exponential growth.

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