Differential Pathomechanisms of Desmoglein 1 Transmembrane Domain Mutations in Skin Disease.

Dominant and recessive mutations in the desmosomal cadherin, desmoglein (DSG) 1, cause the skin diseases palmoplantar keratoderma (PPK) and severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, respectively. In this study, we compare two dominant missense mutations in the DSG1 transmembrane domain (TMD), G557R and G562R, causing PPK (DSG1) and SAM syndrome (DSG1), respectively, to determine the differing pathomechanisms of these mutants. Expressing the DSG1 mutants in a DSG-null background, we use cellular and biochemical assays to reveal the differences in the mechanistic behavior of each mutant.

Desmoplakin and clinical manifestations of desmoplakin cardiomyopathy.

Desmoplakin (DSP), encoded by the DSP gene, is the main desmosome component and is abundant in the myocardial tissue. There are three DSP isoforms that assume the role of supporting structural stability through intercellular adhesion. It has been found that DSP regulates the transcription of adipogenic and fibrogenic genes, and maintains appropriate electrical conductivity by regulating gap junctions and ion channels.

Novel Compound Heterozygous Mutations in Gene in a Chinese Family with Papillon-Lefevre Syndrome.

Papillon-Lefevre syndrome (PLS) (OMIM: 245000) is a rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and early onset periodontitis, resulting in the premature loss of the deciduous and permanent teeth. PLS is caused by mutations in the cathepsin C () gene (OMIM: 602365), which has been mapped to chromosome 11q14-q21. Genetic analysis can help early and rapid diagnosis of PLS.

RSPO1-mutated fibroblasts from non-tumoural areas of palmoplantar keratoderma display a cancer-associated phenotype.

R-spondin (RSPO)1 is a fibroblast-secreted protein that belongs to the R-spondin protein family which is essential for reproductive organ development, epithelial stem cell renewal and cancer induction or suppression. RSPO1 gene mutations cause palmoplantar hyperkeratosis with squamous cell carcinoma (SCC) of the skin, 46XX sex reversal and true hermaphroditism. To characterize RSPO1-deficient skin fibroblasts derived from two patients with mutations in RSPO1, with palmoplantar hyperkeratosis, recurrent SCC and 46XX sex reversal, to provide further insight into disease-related skin tumourigenesis.

Hyperpigmentation in a Chinese family with autosomal dominant Cole disease.

Cole disease (OMIM 615522), caused by mutations in ENPP1, is a rare autosomal dominant or recessive genodermatosis characterized by guttate hypopigmentation and punctate palmoplantar keratoderma. To date, a few cases with autosomal recessive inheritance had been reported with hyperpigmentation. The aim of this case report was to investigate the molecular basis of individuals with hyperpigmentation, hypopigmentation and punctate keratoderma in a Chinese family.

Aquagenic (pseudo) keratoderma (aquagenic palmoplantar keratoderma, aquagenic wrinkling of palms).

Aquagenic palmoplantar keratoderma (APK) is an uncommon hereditary or sporadic condition that is characterized by edematous flat-topped papules appearing on palmar skin with wrinkling after brief water exposure. APK has been associated with cystic fibrosis (CF), presenting with the same mutations found in CF (usually ΔF508 of the CFTR gene), either homozygous or heterozygous. APK may be idiopathic or drug-induced.

"Oral Manifestations of Patients with Inherited Defect in Phagocyte Number or Function" a systematic review.

Introduction: Inherited phagocyte defects are one of the subgroups of primary immunodeficiency diseases (PIDs) with various clinical manifestations. As oral manifestations are common at the early ages, oral practitioners can have a special role in the early diagnosis.

Materials And Methods: A comprehensive search was conducted in this systematic review study and data of included studies were categorized into four subgroups of phagocyte defects, including congenital neutropenia, defects of motility, defects of respiratory burst, and other non-lymphoid defects.

Effectiveness of a cosmetic device containing a combination of alpha- and beta-hydroxy acids, urea, and thuja for the treatment of seborrheic keratoses.

Background: Seborrheic keratosis is a benign epidermal tumor of cosmetic concern-as it progressively increases in size, thickness, and pigmentation-on which topical treatments are poorly effective. Considering its keratotic component, effective products may include active principles with keratolytic action.

Aims: Evaluate the efficacy and tolerability of a topical cosmetic product with urea and hydroxy acids, in the treatment of seborrheic keratoses.

[Analysis of clinical feature and genetic basis of a rare case with Olmsted syndrome].

Objective: To analyze the clinical and genetic characteristics of a patient featuring autosomal dominant Olmsted syndrome.

Methods: Clinical features of the patient was reviewed. High-throughput sequencing was carried out to detect potential genetic variants.

Palmo-plantar hyperkeratosis associated with HTLV-1 infection: a case report.

Background: Palmoplantar hyperkeratosis is a cutaneous manifestation that had not been clearly associated with infection by the human T-cell lymphotropic virus, which is a retrovirus that in most cases does not develop clinical pathologies and its symptoms may be undetected. The skin is one of the most affected organs, however until now only seborrheic dermatitis, xerosis/ichthyosis and infective dermatitis associated with HTLV-1 have been described as cutaneous clinical manifestations of this disease.

Case Presentation: We present the case of a 36-year-old male patient with serologically documented HTLV-1 infection, who presented symptoms of diarrhea, malabsorption due to Strongyloides stercoralis, and in whom a physical examination revealed an association with generalized xerosis and palmoplantar keratoderma confirmed by skin biopsy.

Molecular dynamics study of water transport through AQP5-R188C mutant causing palmoplantar keratoderma (PPK) using the gating mechanism concept.

It is widely known that any disruption to the water regulation in aquaporins (AQPs) leads to numerous important diseases. However, studies of dynamics and energetics of disease-causing mutations in the aquaporins on the molecular level are still limited. In the present work, the effects of a skin disease-causing mutant, R188C, on the structure of AQP5 and water transport mechanism within this mutated aquaporin are investigated using the concept of gating mechanism.

Aquagenic Keratoderma: Treatment Update.

Aquagenic keratoderma is an uncommon acquired dermatosis characterized by edema and whitish-translucent papules triggered by immersion or contact with water. Cases have been described in association with certain medications, hyperhidrosis, and cystic fibrosis. The aim of this review is to evaluate the effectiveness of different treatments for aquagenic keratoderma.

Japanese guidelines for the management of palmoplantar keratoderma.

Palmoplantar keratoderma (PPK) is a collective term for keratinizing disorders in which the main clinical symptom is hyperkeratosis on the palms and soles. To establish the first Japanese guidelines approved by the Japanese Dermatological Association for the management of PPKs, the Committee for the Management of PPKs was founded as part of the Study Group for Rare Intractable Diseases. These guidelines aim to provide current information for the management of PPKs in Japan.

Genotype‒Structurotype‒Phenotype Correlations in Patients with Pachyonychia Congenita.

Pachyonychia congenita (PC) is a genetic disorder of keratin that presents with nail dystrophy, painful palmoplantar keratoderma, and other clinical manifestations. We investigated the genotype‒structurotype‒phenotype correlations seen with mutations in keratin genes (keratin [K]6A, K6B, K6C, K16, K17) and utilized protein structure modeling of high-frequency mutations to examine the functional importance of keratin structural domains in PC pathogenesis. Participants of the International PC Research Registry underwent genetic testing and completed a standardized survey on their symptoms.

Epidemiological aspects of superficial fungal infections in Koranic schools in two localities of Senegal (Thies and Touba).

Background: In developing countries, superficial fungal infections (SFI) are endemic and cause a therapeutic problem because of the duration and cost of treatment. Community living and promiscuity are key factors in the direct or indirect transmission and spread of these diseases.

Objectives: The objective was to study the epidemiological aspects of SFI, among koranic school children in two localities in Senegal.

Generation and Characterization of a CRISPR/Cas9-Mediated Knockout in Human Fibroblasts.

Loss-of-function mutations in the synaptosomal-associated protein 29 (SNAP29) lead to the rare autosomal recessive neurocutaneous cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK) syndrome. SNAP29 is a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. So far, it has been shown to be involved in membrane fusion, epidermal differentiation, formation of primary cilia, and autophagy.