Expanding the Genotypic Spectrum of Bathing Suit Ichthyosis.

Importance: Bathing suit ichthyosis (BSI) is a rare congenital disorder of keratinization characterized by restriction of scale to sites of relatively higher temperature such as the trunk, with cooler areas remaining unaffected. Fewer than 40 cases have been reported in the literature. Bathing suit ichthyosis is caused by recessive, temperature-sensitive mutations in the transglutaminase-1 gene (TGM1). Clear genotype-phenotype correlations have been difficult to establish because several of the same TGM1 mutations have been reported in BSI and other forms of congenital ichthyosis. We identify novel and recurrent mutations in 16 participants with BSI. Objective: To expand the genotypic spectrum of BSI, identifying novel TGM1 mutations in patients with BSI, and to use BSI genotypes to draw inferences about the temperature sensitivity of TGM1 mutations. Design, Setting, and Participants: A total of 16 participants with BSI from 13 kindreds were identified from 6 academic medical centers. A detailed clinical history was obtained from each participant, including phenotypic presentation at birth and disease course. Each participant underwent targeted sequencing of TGM1. Main Outcomes and Measures: Phenotypic and genotypic characteristics in these patients from birth onward. Results: Of the 16 participants, 7 were male, and 9 were female (mean age, 12.6 years; range, 1-39 years). We found 1 novel TGM1 indel mutation (Ile469_Cys471delinsMetLeu) and 8 TGM1 missense mutations that to our knowledge have not been previously reported in BSI: 5 have been previously described in non-temperature-sensitive forms of congenital ichthyosis (Arg143Cys, Gly218Ser, Gly278Arg, Arg286Gln, and Ser358Arg), and 3 (Tyr374Cys, Phe495Leu, and Ser772Arg) are novel mutations. Three probands were homozygous for Arg264Trp, Arg286Gln, or Arg315Leu, indicating that these mutations are temperature sensitive. Seven of 10 probands with a compound heterozygous TGM1 genotype had a mutation at either arginine 307 or 315, providing evidence that mutations at these sites are temperature sensitive and highlighting the importance of these residues in the pathogenesis of BSI. Conclusions and Relevance: Our findings expand the genotypic spectrum of BSI and the understanding of temperature sensitivity of TGM1 mutations. Increased awareness of temperature-sensitive TGM1 genotypes should aid in genetic counseling and provide insights into the pathophysiology of TGM1 ichthyoses, transglutaminase-1 enzymatic activity, and potential therapeutic approaches.

Trichloroacetic acid peeling versus dermabrasion: a histometric, immunohistochemical, and ultrastructural comparison.

BACKGROUND: Trichloroacetic acid (TCA) chemical peel and dermabrasion are beneficial methods for treatment of photoaged skin. OBJECTIVE: In this study, we evaluated the changes induced by these therapies on various structures of facial skin of nine dark-skinned patients (Fitzpatrick types IV-V; TCA, five patients; dermabrasion, four patients) demonstrating different degrees of photodamage. METHODS: Routine histopathology coupled with histometric computer-assisted image analysis was used to assess epidermal changes. Alcian blue stain was used to evaluate changes in glycosaminoglycans. Immunoperoxidase techniques with antibodies against types I and III collagen and elastin were used to evaluate quantitatively changes in collagen and elastic fibers, and their ultrastructure was examined by transmission electron microscopy. RESULTS: Similar histologic, immunohistochemical, as well as ultrastructural changes were observed in the two groups, including epidermal and dermal rejuvenation with new collagen deposition and normalization of the elastic tissue. However, these changes were more prominent in patients treated with dermabrasion than those treated with TCA. CONCLUSION: The results of this study suggest that beneficial effects of such modalities on facial skin were accomplished primarily by increasing the amounts of collagen I and collagen III and improving the morphologic appearance of collagen and elastic fibers.

Effect of topical tretinoin, chemical peeling and dermabrasion on p53 expression in facial skin.

The tumour suppressor protein p53 is a phosphoprotein that is activated by DNA damage. It is involved in the decision whether the cells should stop replication and proceed to repair their DNA, or to die by apoptosis. In the present study, we evaluate the effect of some treatment modalities on the expression of p53 in facial skin. Biopsy specimens were obtained from the facial skin of 20 patients before and after treatment using topical tretinoin (11 cases), TCA chemical peeling (5 cases) and dermabrasion (4 cases). Biopsy specimens were also obtained from 12 control subjects representing the same age groups of the patients. Topical tretinoin therapy was found to induce a significant decrease in the expression of p53 up to 6 months of therapy followed by a significant increase after 10 months of therapy. On the contrary, superficial TCA peeling did not induce any statistically significant change in the expression of p53. On the other hand dermabrasion was found to induce a significant decrease in the level of expression of p53 in biopsies obtained after complete re-epithelialization followed by a significant increase. These changes in the expression of p53 may play a role in mediating the effects of such treatment modalities on the epidermis, as well as prevention of actinic neoplasia by adjusting any disturbance in the proliferation/apoptosis balance observed in photoaged facial skin.

Type 1 segmental manifestation of Hailey-Hailey disease.

Two types of mosaic manifestations can be distinguished in autosomal dominant skin disorders. A type-1 mosaicism reflects a localized postzygotic mutation in an otherwise normal embryo. This mutation leads to a localized population of heterozygous cells, resulting in segmental disease. In contrast, a type-2 mosaicism represents a postzygotic mutation eliminating the normal allele at a gene locus, for which the embryo carries a dominant heterozygous germline mutation. The corresponding phenotype is characterized by segmental lesions superimposed on "classical" disease. The authors describe the clinical and histopathologic aspects of the first case of type-1 segmental manifestation of Hailey-Hailey disease.