A case of poikiloderma with neutropenia caused by USB1 gene mutations / 中华皮肤科杂志

A female patient aged 3 years and 1 month developed poikilodermatous patches on the right forearm at the age of 6 months, which spread to bilateral cheeks, buttocks and limbs at the age of 1 year and 4 months. Skin examination showed multiple brown and off-white poikilodermatous patches on the bilateral cheeks, buttocks and limbs, which were intermingled with normal skin and did not merge with each other. The trunk and oral mucosa were not involved. The fifth toenail of the right foot was thickened. Blood routine examination showed that the neutrophil count fluctuated between 1.70 × 10 9/L and 9.32 × 10 9/L. Histopathological examination of the brown patches on the left upper limb showed hyperpigmentation in the basal layer of the epidermis, and a few melanophages around the dermal vessels. Next-generation sequencing of peripheral blood genomic DNA revealed two compound heterozygous mutations c.798A>G in exon 7 and c.479delT in exon 3 of the USB1 gene in the child, which were inherited from her father and mother respectively. Neither of the two mutations was identified in 100 unrelated healthy controls. The patient was diagnosed with poikiloderma with neutropenia.

Autosomal recessive dyskeratosis congenita: a case report and TERT gene mutation analysis / 中华皮肤科杂志

Objective:To report a case of autosomal recessive dyskeratosis congenita, and to detect mutations in its causative genes.Methods:Peripheral blood samples were collected from the proband and her parents, genomic DNA was extracted, and 100 unrelated healthy individuals served as controls. The Illumina Nextseq500 sequencer was used to detect sequence variations in coding regions of exons of the skin disease-related genes in the proband′s family, and the causative mutation was verified by PCR-Sanger sequencing. The conservation and pathogenicity of gene mutation sites and corresponding protein structure changes were predicted by using bioinformatics softwares Clustalw2.0, PyMOL, PolyPhen-2, SIFT and FATHMM.Results:The proband clinically presented with reticular poikilodermatous patches on the neck and chest, punctate pigmentation on the axilla, atrophy of some toenails, rough skin and oral leukoplakia, accompanied by abnormality in some indicators of routine blood tests and liver function. Genetic testing showed that the proband carried compound heterozygous mutations c.2452G>A (p.Val818Met) and c.2594G>A (p.Arg865His) in the TERT gene, and the c.2452G>A mutation was not included in the Human Gene Mutation Database. The proband′s mother carried a heterozygous mutation c.2452G>A, and no mutation was identified in the TERT gene of her father or 100 healthy controls. Bioinformatics analysis showed that the amino acid positions 818 and 865 of TERT proteins in multiple species were highly conserved and completely conserved respectively, and the corresponding protein structures changed after the above gene mutations. Based on the clinical manifestations, genetic testing, auxiliary examinations, and bioinformatics analysis results, the patient was finally diagnosed with autosomal recessive dyskeratosis congenita.Conclusion:The compound heterozygous mutations c.2594G>A (p.Arg865His) and c.2452G>A (p.Val818Met) in the TERT gene may be responsible for the clinical phenotype of the proband.

A case of Carvajal syndrome caused by a spontaneous mutation in the desmoplakin gene / 中华皮肤科杂志

Objective@#To report a case of Carvajai syndrome caused by a spontaneous mutation in the desmoplakin (DSP) gene.@*Methods@#Clinical data were collected form a patient with Carvajal syndrome in Department of Dermatology, The First Affiliated Hospital of Zhengzhou University. Peripheral blood samples were obtained from the proband, his parents and 100 unrelated healthy controls, and blood genomic DNA was extracted. The ion torrent PGM second-generation sequencing platform was used to detect sequence variations in coding regions of exons in skin disease-related genes in the proband and his parents, and the pathogenic variation was verified by PCR-Sanger sequencing.@*Results@#The proband clinically presented with woolly hair, diffuse palmoplantar keratoderma, onychodysplasia, hypodontia and sinus arrhythmia as shown by electrocardiogram. Gene sequencing revealed a heterozygous missense mutation c.1790C>T (p.Ser597Leu) in exon 14 of the DSP gene in the proband, resulting in the substitution of serine by leucine at amino acid position 597. No mutation was identified in the proband′s parents or the 100 healthy controls, so the mutation in the proband is spontaneous. The patient was finally diagnosed with Carvajal syndrome according to the clinical manifestations, gene detection and auxiliary examination results.@*Conclusion@#The heterozygous missense mutation C.1790C>T (p.Ser597Leu) of the DSP gene may be the pathogenic mutation for the clinical phenotype of the patient.

Desmoglein 4 gene mutation analysis in a pedigree with autosomal recessive hereditary monilethrix / 中华皮肤科杂志

A 3-year-old female proband presented with patchy follicular keratotic papules on the hairless scalp after birth. At about the age of 2 years, sparse hairs of non-uniform thickness began to grow, but they fell out intermittently and were broken easily. Some eyebrows and eyelashes of different lengths fell out or were broken. Physical examination revealed good condition of nutrition, normal height, weight and intelligence, with no obvious abnormalities in other systems. Skin examination showed sparse and broken hairs with follicular keratotic papules on the vertex and occiput. Teeth, nails, toenails and sweat glands were normal. Dermoscopy, optical microscopy and scanning electron microscopy all showed that affected hairs gave a beaded appearance. Gene sequencing showed that the proband carried heterozygous deletions of exons 2-16 in the desmoglein 4 (DSG4) gene, and a heterozygous mutation c.574T>C (p.S192p) (NM-177986) in the DSG4 gene, which were inherited from her father and mother respectively. None of the above mutations in the DSG4 gene were found in 100 healthy controls. According to the gene sequencing results and clinical phenotype, the patient was finally diagnosed with autosomal recessive hereditary monilethrix, and the c.574T>C mutation and heterozygous deletions of exons 2-16 of the DSG4 gene may contribute to autosomal recessive hereditary monilethrix in the child.

Desmoglein 4 gene mutation analysis in a pedigree with autosomal recessive hereditary monilethrix / 中华皮肤科杂志

A 3-year-old female proband presented with patchy follicular keratotic papules on the hairless scalp after birth.At about the age of 2 years,sparse hairs of non-uniform thickness began to grow,but they fell out intermittently and were broken easily.Some eyebrows and eyelashes of different lengths fell out or were broken.Physical examination revealed good condition of nutrition,normal height,weight and intelligence,with no obvious abnormalities in other systems.Skin examination showed sparse and broken hairs with follicular keratotic papules on the vertex and occiput.Teeth,nails,toenails and sweat glands were normal.Dermoscopy,optical microscopy and scanning electron microscopy all showed that affected hairs gave a beaded appearance.Gene sequencing showed that the proband carried heterozygous deletions of exons 2-16 in the desmoglein 4 (DSG4) gene,and a heterozygous mutation c.574T＞C(p.S192p)(NM-177986) in the DSG4 gene,which were inherited from her father and mother respectively.None of theabove mutations in the DSG4 gene were found in 100 healthy controls.According to the gene sequencing results and clinical phenotype,the patient was finally diagnosed with autosomal recessive hereditary monilethrix,and the c.574T ＞ C mutation and heterozygous deletions of exons 2-16 of the DSG4 gene may contribute to autosomal recessive hereditary monilethrix in the child.

Pyoderma gangrenosum, acne, pyogenic arthritis, and suppurative hidradenitis syndrome: a case study / 中华皮肤科杂志

A 22-year-old male patient visited the Department of Dermatology of the First Affiliated I Iospital of Zbengzhou University on October 31,2016 due to dark red papules,nodules,pustules and cysts on the face,neck,back and in the axillary and inguinal regions for 6 years,and multiple dark purple plaques and ulcers on bilateral lower limbs for 1 year.Six years ago,the patient was diagnosed with acne in other hospital,and no treatment was given.One year ago,multiple purple plaques occurred on the bilateral lower limbs,which then ruptured and progressed into ulcers with diameters of 1-12 cm.On May 9,2002,the patient visited the Department of Pediatric Medicine of the First Affiliated Hospital of Zhengzhou University due to the left knee joint swelling and pain for half a year.Laboratory examination showed negative rheumatoid factor,and smear examination of the left knee joint effusions revealed that there were neutrophils and a small amount of lymphocytes and monocytes in the joint effusions,and no abnormal cells were observed.Then,the patient was diagnosed with pyogenic arthritis of the left knee.Physical examination at admission showed poor general condition,walking difficulty,slightly increased blood pressure of 142/92 mmHg (1 mmHg =0.133 kPa),multiple purple plaques on the bilateral lower limbs with central ulcer formation.Histopathological examination of ulcer margin on the lower limbs showed ulceration,intercellular edema and infiltrating neutrophils in the epidermis,and edema,focal erythrocyte extravasation,diffuse infiltration of neutrophils,lymphocytes and histiocytes in the superficial and middle dermis.Clinical manifestations and pathological features confirmed a diagnosis of pyoderma gangrenosum.There were extensive inflammatory papules,pustules,abscesses and cysts on the face,neck,waist and back,and a small amount of dark red nodules on the axillary and inguinal regions,which were consistent with cystic acne and hidradenitis suppurativa.As PSTPIP1 gene sequencing showed,no mutations were found in exon fragments,while compound heterozygous mutations c.36 + 68 G ＞ A,c.137 + 47 G ＞ C and c.562 + 114 C ＞ G her were found in intron fragments.Among 100 healthy controls,45 carried the same mutations.So,these mutation sites were considered to be polymorphic sites,and the pathogenicity of these mutations was still unclear.Finally,the patient was diagnosed with PAPASH syndrome.The patient was treated with methylprednisolone,cefminox,isotretinoin and thalidomide,and the lesions were markedly improved after 2 weeks.Now the patient was still followed up.

A case of blue vitiligo / 中华皮肤科杂志

A 26?year?old male patient presented with facial depigmented patches for 10 years, some of which turned to blue?grey 7 years prior to the presentation. Before the white patches turned blue?gray, the patient developed contact dermatitis due to topical application of self?made drugs. Skin examination showed blue?gray hyperpigmentation on the left upper lip and in the temporal region, with white hairs in the hyperpigmented lesions on the left upper lip. Dermoscopy revealed irregularly shaped, light to dark blue?gray patches on the left upper lip, which were intermingled with white patches in some regions, and white hair stubs were observed in the white patches. Histopathological examination of temporal lesions showed decreased melanocytes in some regions in the epidermis, pigmentation in both basal and suprabasal layers, perivascular infiltration of a small number of chronic inflammatory cells and melanophages in the superficial dermis, and melanophage infiltration around sweat ducts. Finally, the patient was diagnosed with blue vitiligo. He refused to receive any treatments, and follow?up was under way.

Clinical analysis of seven cases of generalized pustular psoriasis of pregnancy / 中华围产医学杂志

Objective To investigate the clinical characteristics,diagnosis,therapy and maternal and perinatal prognosis of generalized pustular psoriasis of pregnancy.Methods Clinical data for seven inpatients with generalized pustular psoriasis of pregnancy were retrospectively analyzed from January 1,2005 to December 31,2012.Results Three patients had family history of psoriasis and five had previous history of psoriasis.All skin lesions were large patches of erythema,with needlepoint to miliary size pustules and scales.Two patients had oral involvement and three had nail involvement.Biopsy and bacterial culture were performed on five patients,in whom histopathological changes of pustular psoriasis were found,and bacterial culture was negative except in one patient.Among the patients,four had confirmed cause of disease; six patients were complicated with fever; four had increased leukocytes; seven had elevated neutrophils and C-reactive protein;five had increased total protein; and six had increased albumin.The disease was diagnosed according to the clinical manifestations and laboratory tests.Comprehensive treatment with glucocorticosteroids,antibiotics and local treatment were performed.Four patients had live births,and three patients underwent odinopoeia.Two babies were healthy,one had died,and another had varus foot deformity.Three patients had pustular relapse after labor.Conclusions Fetal-placental functions of patients with generalized pustular psoriasis of pregnancy should be monitored closely.Early diagnosis,treatment and termination of pregnancy can improve the maternal and perinatal prognosis.

Expressions of heparinase, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 in malignant melanoma / 中华皮肤科杂志

ObjectiveTo investigate the expressions ofheparinase,matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2(TIMP2) in malignant melanoma lesions and their significance.MethodsSkin specimens were obtained from the lesions of 30 patients with malignant melanoma,30 patients with melanocytic nevus and the normal skin of 15 healthy controls.Immunohistochemical SP method was used to detect the protein expression of heparinase,MMP2 and TIMP2.ResultsThe malignant melanoma tissue specimens significantly differed from the melanocytic nevus and control tissue specimens in the expression rate of heparinase (63.33％ vs.6.67％ and 0.00,x2 =21.172,27.805,both P ＜ 0.01 ),MMP2 (70.00％ vs.13.33％ and 0.00,x2 =19.817,19.866,both P＜ 0.01) and TIMP2(60.00％ vs.6.67％ and 0.00,x2 =19.200,15.000,both P ＜ 0.01 ).ConclusionThe expression of heparinase,MMP2 and TIMP2 is significantly higher in malignant melanoma lesions than in melanocytic nevus lesions and normal skin tissue.

Expressions of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 in human malignant melanoma transplanted in nude mice / 中华皮肤科杂志

ObjectiveTo investigate the expressions of matrix metalloproteinase-2 (MMP2) and tissue inhibitor of MMP2 (TIMP2) in human malignant melanoma transplanted subcutaneously in nude mice.Methods A non-sense oligonucleotide (N-ODN) and an antisense oligodeoxynucleotide (ASODN)against heparanase mRNA were designed and synthesized.Cultured human A375 malignant melanoma cells were classified into 4 groups to be transfected with the N-ODN,ASODN of 10,20,30 μmol/L,respectively,via liposomes.The cells receiving no treatment served as the blank control group.Then,the transfected or untransfected cells were subcutaneously inoculated into nude mice.Six weeks after the transplantation,transplanted tumors were removed from the nude mice and subjected to immunohistochemical staining for the detection of MMP2 and TIMP2 protein expressions.ResultsThe protein expressions of MMP2 and TIMP2 were significantly lower in tumor tissue specimens from nude mice inoculated with ASODN-transfected A375 cells than in those with N-ODN-transfected cells and in those with untransfected cells(P ＜ 0.05),significantly different between the tumor tissue specimens from mice inoculated with A375 cells transfected with 10,20 and 30 μmol/L of ASODN (all P ＜ 0.05 ).ConclusionThe ASODN against heparinase displays a marked inhibitory effect on the expressions of MMP2 and TIMP2 proteins in malignant melanoma transplanted in nude mice.

Expressions of stem cell markers CD133,nestin and CD44 in malignant melanoma and their significance / 中华皮肤科杂志

Objective To investigate the expressions of stern cell markers CD133,nestin and CD44 in malignant melanoma and their significance.Methods Tissue samples were obtained from 30 patients with malignant melanoma and 30 patients with intradermal nevus.The expressions of three markers were immunohistochemically detected in the samples.Results In malignant melanoma specimens,the expression rate of CD133,nestin and CD44 was 53.33%(16/30),80.00%(24/30)and 20.00%(6/30),respectively,significantly difierent from that in intradermal nevus specimens [23.33%(7/30),53.33%(1 6/30)and 0,respectively,all P＜0.05].The percentage of cells positive for CD133,nestin and CD44 was 2.98%±5.62%,34.92%±34.89%and 1.28%±3.26%,respectively,in malignant melanoma specimens.0.10%±0.21%,7.26%±13.13%and 0,respectively,in intradermal nevus specimens;there was a significant difierence between the two groups of specimens(all P＜0.05).In malignant melanoma and intradermal nevus,the expression intensity of CD133.nestin and CD44 showed no significant correlation with patients'sex.age or disease course(all P＞0.05).ConclusionsCD133,nestin and CD44 are highly expressed in malignant melanoma,but weakly expressed or absent in intradermal nevus,suggesting that tumor stem cells might exist in malignant melanoma tissue.

Expression of matrix metalloproteinase 7 in malignant melanoma / 中华皮肤科杂志

Objective To study the relationship of matrix metalloproteinase 7(MMP7)expression to the infiltration and metastasis of malignant melanoma.Methods Various concentrations(10,20,30 μmol/L)of heparanase antisense oligodeoxynucleotide (ASODN)was used to transfect human malignant melanoma cell line A375.Then,the transfected cells were subcutaneously inoculated into the right back of nude mice.Six weeks after the inoculation,transplanted tumors were isolated from the mice,and the levels of MMP7 protein expression were assessed by SP immunohistochemistry.The expression rate of MMP7 was also examined by SP immunohistochemistry in A375 cells and in tissue samples from patients with malignant melanoma(n=30),iunctional nevus(n=30)and normal human controls(n=15).Results The expression rate of MMP-7 was 83.33%(25/30),6.67%(2/30)and 0(0/15)respectively in malignant melanoma,iunctional nevus and normal skin tissue samples;there was a significant difierence in the positivity rate of MMP-7 between the malignant melanoma group and iunctional nevus group (x2=35.62,P=0.000)as well as normal control group(x2=28.12,P=0.000),but not between the junctional nevus group and normal control group(P＞0.05).The expression of MMP-7 in transplanted tumor was decreased to a varying degreee by three levels of ASODN,and the inhibitory effects of 30 mol/L ASODN were the strongest(P＜0.05).MMP-7 protein was also highly expressed in A375 cells.Conclusions The expression of MMP-7 in cutaneous malignant melanoma is higher than that in iunctional nevus and normal skin tissue.Hpa-ASPDN significantly inhibits the expression of MMP-7 in transplanted tumors in nude mice.MMP-7 is highly expressed in A375 cells.