Detection of ATP2C1 gene mutations in a family with generalized familial benign chronic pemphigus / 中华皮肤科杂志

A 60-year-old female proband presented with recurrent erythema, blisters and erosions all over the body for 30 years, which had been aggravated 10 days prior to the presentation. Skin examination showed erythematous swelling of the bilateral eyelids with scattered dark red crusts, scattered erythema and erosions on the nasolabial folds and chin, large areas of erythema and erosions on the neck, bilateral axillae, left cubital fossa, perineum and perianal area, accompanied by bright red granulation tissues and positive Nikolsky′s sign. The proband had two sons, both of whom occasionally presented with erythema and erosions on the axillae and groin, and had not been diagnosed or treated. Blood samples were collected from the proband and her two sons, and genomic DNA was extracted and subjected to whole-exome sequencing. A heterozygous deletion mutation c.955_957del (p.A319del) was identified in the ATP2C1 gene in the proband and her two sons, which had not been previously reported. The patient was finally diagnosed with generalized familial benign chronic pemphigus.

Gene mutation analysis in a Chinese pedigree with autosomal dominant Waardenburg syndrome / 中华皮肤科杂志

Objective:To report a Chinese pedigree with autosomal dominant Waardenburg syndrome, and to identify causative gene mutations.Methods:Clinical data and peripheral blood samples were collected from the proband and her parents. Genomic DNA was extracted, gene mutations were detected through a next-generation skin-targeted sequencing panel, and Sanger sequencing was performed to verify causative mutations.Results:The proband clinically presented with irregular white patches on the abdomen and lower limbs, moderate to severe sensorineural deafness in the right ear, and iris heterochromia in both eyes. The proband′s mother presented with iris heterochromia in both eyes, epicanthus, early canities and thick eyebrows. In the family, both the proband and her mother were diagnosed with Waardenburg syndrome. A causative frameshift mutation c.976-977delinsT (p.Thr327Profs*54) was identified in both the proband and her mother, which caused the AG to TT base substitution at positions 976 - 977 in the coding region of exon 7 of the PAX3 gene, resulted in a frameshift from the amino acid position 327 to 54 in the PAX3 protein (threonine was substituted by proline at amino acid position 327). The proband′s father showed a normal phenotype, and his genetic test results were negative.Conclusion:The novel frameshift mutation c.976-977delinsT (p.Thr327Profs*54) in the PAX3 gene may contribute to the clinical phenotype of the patients with Waardenburg syndrome in the family.

Neonatal linear IgA bullous dermatosis / 中华皮肤科杂志

A 10-day-old male infant presented with skin erythema and blisters for 6 days. Skin examination showed scattered or confluent erythema all over the body, tense blisters of varying sizes on the normal skin or an erythematous base, and some blisters were ulcerated and erosive; bloody bullae and erythematous erosive patches could be seen on the oral mucosa. Histopathological examination revealed subepidermal blisters, and there were some neutrophils and a few eosinophils in the blisters. Direct immunofluorescence assay showed homogeneous linear IgA and granular C3 deposits along the basement membrane zone, without IgG deposits. The diagnosis of neonatal linear IgA bullous dermatosis was confirmed. After comprehensive treatments including nutritional support and anti-infection treatment, skin erythema and blisters subsided, and the mucosal damage was attenuated. The telephone follow-up 16 months after discharge showed that the infant was in good general condition with normal growth and development, and the oral mucosal lesions had subsided and healed, without new skin lesions.

Pathologically Elevated-Cyclic Stretch Suppressed Vascular Smooth Muscle Cell Mitochondrial Biogenesis by Down-regulating PGC1α Expression / 医用生物力学

Objective To investigate the effect of pathologically elevated-cyclic stretch induced by hypertension on mitochondrial biogenesis of vascular smooth muscle cells (VSMCs), and the role of PGC1α in this process. Methods The Flexcell-5000T stretch loading system in vitro was applied to VSMCs with a frequency of 1. 25 Hz and an amplitude of 5% or 15% to simulate the mechanical environment under normal physiological or hypertensive pathological conditions respectively. Western blotting and qPCR were used to detect the expression of PGC1α, citrate synthase and mitochondrial DNA (mtDNA) copy number in VSMCs under normal physiological or hypertensive pathological conditions. VSMCs were treated with PGC1α specific activator ZLN005 to promote PGC1α expression or specific interfering fragment siRNA to inhibit PGC1α expression in order to detect the effect on citrate synthase and mtDNA copy number. Results Compared with 5% physiological cyclic stretch, 15% pathologically elevated-cyclic stretch significantly suppressed the expression of PGC1α, citrate synthase and mtDNA copy number in VSMCs. Compared with control group, the protein expression of PGC1α was significantly decreased and increased respectively. When VSMCs transfected with PGC1α siRNA or incubated PGC1α activator ZLN005, the expression of citrate synthase and mtDNA copy number were also significantly down regulated and up-regulated in VSMCs accordingly. Under physiological cyclic stretch conditions, the protein level of PGC1α was significantly down-regulated by PGC1α siRNA, which also significantly down-regulated citrate synthase expression and mtDNA copy number. The protein expression of PGC1α was significantly up-regulated by ZLN005, which also enhanced the expression of citrate synthase and mtDNA copy number. Conclusions The pathological cyclic stretch induced by hypertension significantly down-regulated the expression of citrate synthase and mtDNA copy number via suppressing the expression of PGC1α, resulting in mitochondrial dysfunction of VSMCs. PGC1α may be a potential therapeutic target molecule to alleviate the progression of hypertension.

Mutation analysis of the ADAR gene in two cases of dyschromatosis symmetrica hereditaria and a survey of their families / 中华皮肤科杂志

Objective:To investigate two Chinese pedigrees with dyschromatosis symmetrica hereditaria (DSH) , and to analyze gene mutations in the pedigrees.Methods:Clinical data were collected from two probands with DSH and other family members in their pedigrees. Peripheral blood samples were obtained from the two probands, their parents and 100 unrelated healthy controls. Gene mutations were detected by using a skin-targeted sequencing panel, and then verified by Sanger sequencing.Results:Case 1, an 18-year-old male patient, presented with millet-sized hyperpigmented and hypopigmented macules scattered on the dorsum of both hands and feet at the age of 5 years, and his mother had similar manifestations. A novel heterozygous frameshift mutation c.1970dupT (p.F657fs) was identified in exon 5 of the ADAR gene in case 1 and his mother, but not found in his father. Case 2, an 8-year-old male patient, presented with mottled rice- to soybean-sized brown hyperpigmented macules and hypopigmented macules on the face and neck, lower back, buttocks, lower limbs, as well as hands and feet, and his father presented with similar manifestations. A known heterozygous frameshift mutation c.2433_2434delAG (p.T811fs) was identified in exon 7 of the ADAR gene in case 2 and his father, but not found in his mother. Neither of the two mutations was identified in the 100 unrelated healthy controls.Conclusion:In this study, a novel mutation c.1970dupT (p.F657fs) in the ADAR gene was identified in a patient with DSH.

Variation of COL7A1 gene in dystrophic epidermolysis bullosa pruriginosa / 中华医学遗传学杂志

OBJECTIVE@#To perform gene mutation analysis in a Chinese pedigree with dystrophic epidermolysis bullosa pruriginosa (DEB-Pr), and explore phetotype, genotype, and genotypes-phenotypes relationship of DEB-Pr.@*METHODS@#Potential variants of the COL7A1 gene were detected by skin targeted sequencing panel and verified by Sanger sequencing. The pathogenicity of the variation was analyzed.@*RESULTS@#Compound heterozygous variants, c.4128delT and c.8234G>A, were detected in the COL7A1 gene of the two patients. The c.4128delT(p.Pro1376fs) variant was derived from their mother and unreported previously. According to the American College of Medical Genetics and Genomics Standards and Guidelines, it was suggested to be a pathogenic mutation. The c.8234G>A(p.Arg2745Gln) variant was derived from their father, and possibly is a pathogenic variation.@*CONCLUSION@#In this study, the compound heterozygous variants of c.4128delT(p.Pro1376fs) and c.8234G>A(p.Arg2745Gln) of the COL7A1 gene probably underlies the disease in this patient and his sister. And our study expands the database on mutations of DEB-Pr.

Gene mutation analysis in a Chinese pedigree with autosomal recessive woolly hair / 中华皮肤科杂志

Objective:To identify causative genes for autosomal recessive woolly hair (ARWH) in a family.Methods:Clinical data were collected from two patients and other family members in a Chinese pedigree of Han nationality with ARWH. Peripheral blood samples were obtained from the two patients, their unaffected parents and 100 unrelated healthy individuals, and DNA was extracted from the blood samples. A next-generation skin-targeted sequencing panel was used to detect gene mutations in the patients, and Sanger sequencing was performed to verify the sequencing results. The function of protein encoded by the mutant gene was predicted.Results:Two missense mutations c.530T>G (p.Leu177Arg) and c.736T>A (p.Cys246Ser) were both identified in the LIPH gene of the two patients, which were inherited from their father and mother respectively. Neither of the two mutations was identified in the 100 unrelated healthy controls. Interspecies sequence alignment showed that leucine at amino acid position 177 and cysteine at amino acid position 246 of the protein encoded by the LIPH gene were highly evolutionarily conserved. As SIFT and Polyphen-2 softwares showed, the mutations c.530T>G (p.Leu177Arg) and c.736T>A (p.Cys246Ser) were both predicted to be detrimental variations.Conclusion:Two missense mutations c.530T>G (p.Leu177Arg) and c.736T>A (p.Cys246Ser) in the LIPH gene may contribute to the clinical phenotype of the two patients with ARWH in this family.

Genetic testing and genotype-phenotype analysis for a child with X-linked hypohidrotic ectodermal dysplasia / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing for a Chinese patient with X-linked hypohidrotic ectodermal dysplasia (XLHED) and explore its genotype-phenotype correlation.@*METHODS@#Clinical data of the patient was collected. Peripheral blood samples were taken from the patient, his parents and 100 unrelated healthy controls. Genetic variants were detected by using next-generation sequencing using a skin-disease panel through targeted capture and next generation sequencing. Candidate variant was verified by Sanger sequencing. All literature related to genetic testing of XLHED patients in China was searched in the database, and the genotypes and phenotypes of patients in the literature and the correlation between them were statistically analyzed.@*RESULTS@#A novel splice site variant c.655_689del was detected in the patient but not among his parents and the 100 unrelated healthy controls. So far 61 variants of the EDA gene have been identified among Chinese patients with XLHED, which suggested certain degree of genotype-phenotype correlation.@*CONCLUSION@#A novel c.655_689del variant has been identified in the EDA gene, which has expanded the spectrum of EDA gene variant and facilitated delineation of the genotype-phenotype correlation of XLHED.

Carbamazepine-induced toxic epidermal necrolysis in a patient with HLA-A*31:01 allele / 中华皮肤科杂志

Objective:To detect susceptibility genes for toxic epidermal necrolysis (TEN) caused by carbamazepine in a patient.Methods:Clinical data and peripheral blood samples were collected from a patient with carbamazepine-induced TEN. DNA was extracted from the peripheral blood samples, fluorescence in situ hybridization was performed to detect susceptibility gene loci for carbamazepine-induced TEN, including HLA-A*31:01 (rs1633021), HLA-B*58:01 (rs3095318), HLA-B*15:02 (rs3909184) and HLA-B*15:02 (rs2844682) . Results:The 40-year-old female patient of Han nationality presented with perioral erythema and blisters for 7 days, which had spread all over the body for 4 days. The patient had been treated with carbamazepine for 1 month before the occurrence of skin lesions. Genetic testing showed that the patient was negative for HLA-B*15:02 allele, but positive for HLA-A*31:01 allele.Conclusion:The Chinese patient of Han nationality with carbamazepine-induced TEN was positive for HLA-A*31:01 allele.

Adalimumab in the treatment of severe plaque psoriasis: a clinical observation / 中华皮肤科杂志

Objective:To evaluate the efficacy and safety of adalimumab in the treatment of severe plaque psoriasis.Methods:From June 2018 to April 2019, 20 patients with severe plaque psoriasis were collected from Department of Dermatology, Henan Provincial People′s Hospital. After initial subcutaneous injection of adalimumab at a dose of 80 mg, these patients were subcutaneously injected with adalimumab at a dose of 40 mg at weeks 1, 3, 5, 7, 9 and 11. At weeks 4, 8 and 12, psoriasis area and severity index (PASI) was recorded, and changes in skin lesions were observed by reflectance confocal microscopy (RCM) . Adverse reactions were monitored during treatment.Results:At week 4, 12 patients achieved a 50% reduction in PASI (PASI50) ; at week 8, 14 achieved PASI75; at week 12, 20 patients achieved PASI75, of which 5 achieved PASI90 and 2 achieved PASI100. As RCM showed, the melanin content in the basal layer of skin lesions was lower compared with that of perilesional normal skin before treatment, gradually increased within 4 weeks, and nearly returned to normal at week 12. No infections, tumors or other related adverse reactions occurred in the 20 patients.Conclusion:Subcutaneous injection of adalimumab every other week is markedly effective in the treatment of severe psoriasis, with few related adverse reactions.

Two cases of Darier′s disease: ATP2A2 gene mutation analysis and a family survey / 中华皮肤科杂志

Case 1, a 16-year-old male patient, presented with local verrucous hyperplasia and clustered brown follicular keratotic papules on the face, neck and bilateral axillae, some of which merged into plaques; his mother had similar medical history and clinical manifestations. Case 2, a 21-year-old male patient, presented with local verrucous hyperplasia and diffuse follicular keratotic papules on the head, face, neck, trunk, bilateral axillae and buttocks, some of which merged into patchy lesions; none of his family members had similar symptoms. Histopathological examination of the neck skin lesion of the case 2 showed epidermal hyperkeratosis with focal parakeratosis, suprabasal cleft with acantholysis, "villi" , corps ronds and grains in the spinous layer, and inflammatory cells infiltrating the superficial dermis. Genetic testing showed a missense mutation c.2300A>G in exon 15 of the ATP2A2 gene in both the case 1 and his mother, and a splice-region mutation c.2097+5G>A at the junction between exon 15 and intron 15 of the ATP2A2 gene in the case 2. Neither of these mutations were identified in the other family members of the 2 patients.

Short-term efficacy and safety of secukinumab in the treatment of moderate to severe plaque psoriasis: a clinical observation / 中华皮肤科杂志

Objective:To evaluate the short-term clinical efficacy and safety of secukinumab in the treatment of moderate to severe plaque psoriasis.Methods:Thirty-six patients with moderate to severe psoriasis, who visited Department of Dermatology, Henan Provincial People′s Hospital from June 2019 to November 2019, received subcutaneous injection of secukinumab at a dose of 300 mg once a week for 5 weeks, followed by once every 4 weeks. Psoriasis area and severity index (PASI) was recorded at weeks 4, 8 and 12, and adverse drug reactions were observed during the treatment.Results:All the 36 patients received the treatment for at least 12 weeks. At week 4, 8 patients achieved PASI75, including 3 achieving PASI90 and 1 achieving PASI100; at week 8, 26 achieved PASI75, of which 16 achieved PASI90 and 4 achieved PASI100; at week 12, 32 achieved PASI75, of which 26 achieved PASI90 and 8 achieved PASI100. No patients had serious adverse drug reactions, such as severe infections or malignancies. One patient developed abdominal pain and distension after subcutaneous injection in the abdomen, and the symptoms disappeared after 3 days; 1 patient developed tonsillitis followed by eczema-like lesions on the original psoriaitc lesions; suppurative lymphadenitis occurred in the neck of another patient.Conclusion:Secukinumab is markedly effective in the treatment of moderate to severe plaque psoriasis with few adverse effects, and is a new treatment option for patients with moderate to severe plaque psoriasis.

Seven cases of vitiligo caused by eyebrow tattooing / 中华皮肤科杂志

Objective:To report 7 cases of vitiligo caused by eyebrow tattooing.Methods:Seven cases of vitiligo caused by eyebrow tattooing were collected from Department of Dermatology, Henan Provincial People′s Hospital from December 2017 to May 2019, and their clinical features were retrospectively analyzed.Results:One month to 1 year after eyebrow tattooing, several eyebrows became white in the 7 patients. In the early stage, only several eyebrows became white, and the surrounding skin was normal, but white patches with unclear boundaries gradually appeared around the eyebrows in the later stage. Reflectance confocal scanning microscopy of skin lesions on the eyebrow showed depigmentation in the basal layer and around hair follicles, and highly refractive amorphous substances (colorants) in the superficial and middle dermis. The 7 patients all showed negative patch test reactions to eyebrow colorants but positive reactions to sodium dodecyl sulfate.Conclusion:No depigmentation was observed on the eyebrow skin in the early stage of vitiligo caused by eyebrow tattooing, and reflectance confocal scanning microscopy of eyebrow lesions may be beneficial in reducing its misdiagnosis.

Mutation analysis in a pedigree with Rothmund-Thomson syndrome / 中华皮肤科杂志

Objective To detect gene mutations in a pedigree with Rothmund-Thomson syndrome (RTS).Methods Clinical data were collected from two patients (an older sister and a younger brother)and their family members in a Chinese pedigree of Han nationality with RTS.Blood samples were obtained from the two patients,their unaffected older brother,their parents and 100 unrelated healthy controls.DNA was extracted,and all the exons in the encoding area of the RECQL4 gene were amplified by PCR.Gene mutations were detected by a skin-targeted next-generation sequencing panel,and verified by Sanger sequencing.Results Two heterozygous mutations were identified in the RECQL4 gene of the two patients,including a splice site mutation c.2886-1G＞A and an insertion mutation c.1013_1014insC,which were inherited from the father and mother of the patients respectively.Meanwhile,neither of the two mutations was observed in 100 unrelated healthy controls or the older brother of the patients.Conclusion The splice site mutation c.2886-1G＞A and the insertion mutation c.1013_1014insC in the RECQL4 gene may contribute to the clinical phenotype of the patients in this pedigree with RTS.

Mutation analysis in a pedigree with Rothmund-Thomson syndrome / 中华皮肤科杂志

Objective@#To detect gene mutations in a pedigree with Rothmund-Thomson syndrome (RTS) .@*Methods@#Clinical data were collected from two patients (an older sister and a younger brother) and their family members in a Chinese pedigree of Han nationality with RTS. Blood samples were obtained from the two patients, their unaffected older brother, their parents and 100 unrelated healthy controls. DNA was extracted, and all the exons in the encoding area of the RECQL4 gene were amplified by PCR. Gene mutations were detected by a skin-targeted next-generation sequencing panel, and verified by Sanger sequencing.@*Results@#Two heterozygous mutations were identified in the RECQL4 gene of the two patients, including a splice site mutation c.2886-1G>A and an insertion mutation c.1013_1014insC, which were inherited from the father and mother of the patients respectively. Meanwhile, neither of the two mutations was observed in 100 unrelated healthy controls or the older brother of the patients.@*Conclusion@#The splice site mutation c.2886-1G>A and the insertion mutation c.1013_1014insC in the RECQL4 gene may contribute to the clinical phenotype of the patients in this pedigree with RTS.

Analysis of keratin 1 gene mutation and phenotypes in a pair of twins with bullous congenital ichthyosiform erythroderma / 中华皮肤科杂志

Objective To identify mutations in keratin genes (KRT1 and KRT10) in a pair of twins with bullous congenital ichthyosiform erythroderma (BCIE),and to explore the relationship between the causative genes and phenotypes.Methods Clinical data were collected from a pair of twins with BCIE and their family members.Peripheral blood samples were obtained from the twins,their old brother and parents,and DNA was extracted from these blood samples.Polymerase chain reaction (PCR)was performed to amplify all the coding exons and their flanking sequences of the KRT1 and KRT10 genes,and 100 unrelated healthy persons served as controls.Results The 11-year-old male proband presented with recurrent blisters,hypertrophy and desquamation all over the body for 11 years.His twin brother had similar skin lesions.Skin examination of the proband showed diffuse erythema covered with thick scaly crusts on the trunk and extremities.Blisters,bullae and erosions due to ruptured blisters were observed locally with tenderness on palpation.There were obvious hyperkeratotic and hard lesions on the big joints of the extremities.Diffuse hyperkeratosis could be seen on the palms and soles.A mutation c.591 + 1G ＞ A was identified at position 1 in intron 1 of the KRT1 gene in the twins,but not in the 3 healthy family members or the 100 unrelated healthy controls.Conclusion The mutation c.591 + 1G ＞ A at position 1 in intron 1 of the KRT1 gene may contribute to the clinical phenotype of the twins with BCIE.

Flashlamp-pumped pulsed dye laser (595 nm) for the treatment of port-wine stains: a clinical review of 1560 patients / 中华皮肤科杂志

Objective To evaluate the efficacy and safety of a 595-nm flashlamp-pumped pulsed dye laser in the treatment of patients at different ages with port-wine stains (PWS).Methods A retrospective review was performed in 1560 patients with PWS who had been treated with a 595-nm flashlamp-pumped pulsed dye laser.Treatment parameters were selected according to the age of and types of lesions in patients.Results The total response rate was 76.73％ (1197/1560) in all of the patients.Clinical efficacy of the flashlamppumped pulsed dye laser was closely correlated with patients'age (x2 =83.47,P ＜ 0.01) and types of lesions (x2 =46.30,P ＜ 0.01 ).There was a low incidence of adverse reactions which were well tolerable.Conclusion The 595-nm flashlamp-pumped pulsed dye laser is safe and effective for the treatment of PWS.

Expression of Stat 3, GluT-1 and PCNA in condylomata acuminata / 中华皮肤科杂志

Objective To explore the expression and significance of signal transducer and activator of transcription 3 (Stat 3), glucose transporter protein 1 (GluT-1) and proliferation cell nuclear antigen (PC NA) in lesions of condylomata acuminata (CA). Methods SP immunohistochemistry method was used to measure the expression of Stat 3, GluT-1 and PCNA in tissue samples from 40 cases of CA and 20 normal skin controls. Results The positivity rates of Stat 3, GluT-1 and PCNA were 85.0% (34/40), 87.5% (35/40) and 85.0%(34/40), respectively in CA tissue, 35.0% (7/20), 30.0% (6/20)and 55.0% (11/20),respectively in the control tissue; statistical difference was observed in these rates between the two groups (all P ＜ 0.05). The expression intensity of Stat 3, GluT-1 and PCNA was also higher in CA tissue than that in the controls. In addition, the expression intensity of PCNA was correlated with that of Stat 3 and GluT-1in CA tissue (both P＜ 0.05). Conclusions There is an overexpression of Star 3, GluT-1 and PCNA in CA tissue, and the overexpression of Stat 3 and GluT-1 may be associated with the over-proliferation of CA tissue.

Preparation and Therapeutic Effect of Kangzhi Lotion / 中国药房

OBJECTIVE： To prepare Kangzhi lotion and observe its therapeutic effects on seborrheic dermatitis METHODS： To introduce the ingredients， preparation process and quality control of the lotion RESULTS:The total effective rate of the lotion on seborrheic dermatitis was 90 5％  CONCLUSION： The product is reliable in clinical effect and does not induce adverse reaction