Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients' hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.
Humans ; Connexin 30/genetics* ; Connexins/genetics* ; East Asian People ; Ectodermal Dysplasia/pathology* ; Phenotype

Peroxisome proliferator-activated receptors (PPARs) are widely involved in lipid metabolism, glucose metabolism, cell growth and differentiation, and inflammation in the human body. PPARγ agonists can inhibit skin inflammatory response, protect epidermal barrier function, and repair skin injury. This review summarizes various roles of PPARγ in skin biology, and discusses its function in skin diseases, such as psoriasis and skin tumors.

Psoriasis is a chronic inflammatory skin disease.Its pathogenesis remains unclear,and is currently considered to be co-mediated by heredity,environment and immunity.Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor,which is associated with cancer and autoimmune diseases.STAT3 plays a crucial role in the occurrence of psoriasis by participating in the differentiation of T helper 17 cells,hyperproliferation and abnormal differentiation of keratinocytes,interaction with inflammatory cells,hyperplasia of dermal vessels and other important pathological processes.In recent studies,therapies targeting STAT3 and its upstream Janus kinases (JAK) have shown good efficacy and safety in the management of psoriasis.This review summarizes the association between psoriasis and STAT3,so as to provide evidence for the feasibility of the treatment of psoriasis with targeted inhibition of STAT3.

A case of cytomegalovirus infection with skin lesions as the primary manifestation is reported.A 46-year-old female patient presented with a 3-month history of painful perioral blisters and erosions,and a 6-week history of erythema,blisters and erosions on the left ann.The patient was ever diagnosed with systemic lupus erythematosus and lupus nephritis 12 years prior to the presentation.Systemic lupus erythematosus was exacerbated 5 months prior to this presentation,and glucocorticoids and mycophenolate mofetil were administered.Skin examination revealed irregularly shaped perioral blisters with erosions and crusts,localized patchy erythema with erosion in the center on the flexor aspect of the left forearm,erythema and blisters on the left upper arm,and multiple petechiae and ecchymoses on the abdomen.Histopathological examination of the skin lesion on the left upper limb showed epidermal necrolysis with scattered viral inclusion bodies.Immunohistochemical examination revealed positive staining for cytomegalovirus antigen in giant cells in the necrolytic epidermis.Cytomegalovirus DNA was detected in exudates from lesions.However,cytomegalovirus DNA was not detected in the serum in the initial test,but became positive (8.04 × 103 copies/ml) 1 week later.In addition,anti-cytomegalovirus IgG antibodies were detected in the serum.The patient was diagnosed with cutaneous cytomegalovirus infection.Affter the treatment with both oral and topical ganciclovir,the lesions were improved gradually,followed by severe pulmonary infection,and the patient was finally died of multiple organ failure.

Objective To report a pedigree with tyrosinemia type Ⅱ,and to analyze its causative mutations.Methods Clinical data were obtained from a 10-year-old male proband with tyrosinemia type Ⅱ,and analyzed retrospectively.Blood and urine samples were collected from 19 persons in 3 generations of the pedigree,and the amino acid level was detected in these samples.Genomic DNA was extracted from all of the 19 family members,and mutations in the tyrosine aminotransferase (TAT) gene were detected.Results The patient developed photophobia at 2 months after birth,and the symptom was gradually aggravated after that.At the age of 6 years,ocular pain and photophobia occurred.At the age of 8 years,linear keratotic plaques occurred on his fingertips and soles of both feet,with obvious tenderness.Ophthalmic examination showed no obvious abnormalities in corneal staining or ocular fundus.Skin examination showed multiple linear keratotic plaques on the fingers and soles of both feet.The serum tyrosine level was 825.64 μmol/L,and the level of p-hydroxyphenyllactic acid in urine was 161.4 μmol/L.Genetic testing showed 2 novel mutations,including c.236G ＞ A at position 236 in exon 2 of the TAT gene causing the substitution of glycine by glutamic acid (p.Gly79Glu),and c.1141G ＞ T at position 1141 in exon 10 of the TAT gene leading to the formation of a premature termination codon instead of glutamic acid (p.Glu381*).The proband was the only patient in the family.Some members in the patrilineal family carried the mutation c.1141G ＞ T (p.Glu381*),and some in the maternal family carried the mutation c.236G ＞ A (p.Gly79Glu).Conclusion This is the first case of tyrosinemia type Ⅱ reported in the domestic population,and 2 novel heterozygous mutations were identified in the TAT gene,which may lead to the occurrence of tyrosinemia type Ⅱ in the patient.

Objective To investigate clinical and histopathological features of lichen planopilaris (LPP).Methods The clinical and histopathological findings in 3 cases of LPP were analyzed.Results All the 3 patients were female,and their average age was 49 years.One patient presented with large-area patchy hair loss on the frontal,parietal and occipital region,and 2 patients presented with irregular patchy hair loss on the scalp and skin atrophy.Besides the hair loss,the eyebrows and axillary hairs also lost in 1 patient.Histopathological examination showed liquefaction degeneration of basal cells in the walls of hair follicles and infiltration of lymphocytes.Infiltration of a small number of lymphocytes was also observed around blood vessels and appendages.Conclusions LPP may only affect the scalp,or involve the other sites all over the body.LPP commonly manifests as patchy hair loss on the scalp and skin atrophy,and is pathologically characterized by liquefaction degeneration of basal cells in hair follicles and infiltration of lymphocytes.

Objective To assess the expression pattern of protease-activated receptor 2 (PAR2) in human keratinocytes and to characterize its biological functions in the regulation of skin barrier.Methods Primary human keratinocytes and human N/TERT keratinocytes were used as the subject of this study.The expression and distribution of PAR2 in the keratinocytes were analyzed by using immunoflorescence staining and Western blot.Two different PAR2 agonists,trypsin and a PAR2-activating peptide (AP),as well as a PAR2-antagonistic peptide (H2N-FSLLRY-COOH) and a control peptide were used to induce the activation of PAR2 in the keratinocytes.Then,a fluorescence-based calcium mobilization assay was performed to evaluate the biological function of PAR2.Data were statistically analyzed by one-factor analysis of variance.Results Under normal culture conditions,PAR2 was weakly expressed in keratinocytes,and the expression was unaffected by culture medium composition or culture duration.Calcium mobilization was induced by trypsin of 50-250 nmol/L and the PAR2-activating peptide in a dose-and time-dependent pattern.The maximal activation of PAR2 was observed in keratinocytes treated with the PAR2 agonist HAN-SLIGKV-COOH of 75-250 μmol/L.The PAR2-antagonistic peptide (H2N-FSLLRY-COOH) obviously suppressed the increase in calcium mobilization induced by trypsin,while the control peptide PAR-RAP showed no inductive effect on the PAR2 activation based on the absence of calcium mobilization.The substrate-induced calcium release was complete within 250 seconds,and peaked at 50 seconds after the initial trypsin or PAR-AP stimulation.Moreover,the activation of PAR2 was accompanied by an increase in ERK phosphorylation and elicitation of MAPK signaling pathway in keratinocytes.Conclusions Human keratinocytes positively express PAR2,which can be activated by trypsin and PAR2-activating peptides,and the activation of PAR2 may influence the physiological function of keratinocytes by inducing intracellular calcium release.

A 37-year-old female was admitted to the hospital for an itching and painful subcutaneous nodule with ulceration on the extensor aspect of her left forearm for more than 6 months.The pain was severe,continuous and localized.Systemic and local treatment with antibiotics resulted in no obvious improvement.The lesion had gradually increased in size over the past 6 months and the ulcer had enlarged for 1 month.On examination,a hard infiltrative plaque measuring about 5.5 cm × 4.0 cm with a well-defined margin was seen on the extensor aspect of her left forearm,along with ulceration and some dirty discharge on the surface.The diagnosis of fibrosarcoma,grade Ⅱ was eventually made by a biopsy of the lesion,which revealed increased pigmentation in the basal layer,and tumor tissue was tightly adherent to the epidermis.Dermis and subcutaneous fat layer were infiltrated with various sizes of spindle cells with fine collagen fiber bundles between the cells.Obvious atypia and mitotic figures were easily observed in some of the cells.Immunohistochemical analysis showed moderately positive staining for fibronectin,but negative staining for human melanoma black-45 (HMB45),S100,smooth muscle actin (SMA),Melan-a,high molecular weight cytokeratin (HCK),CD34,CD68 or cytokeratin.Some diseases should be differentiated from this case,including dermatofibrosarcoma protuberans,cutaneous spindle cell squamous carcinoma,atypical fibroxanthoma,malignant fibrous histiocytoma,and so on.