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Zhimiao Lin,
Quan Chen,
Mingyang Lee,
Xu Cao,
Jie Zhang,
Donglai Ma,
Long Chen,
Xiaoping Hu,
Huijun Wang,
Xiaowen Wang, [......],
Xuanzhu Liu,
Liping Guan,
Yiquan Tang,
Haizhen Yang,
Ping Tu,
Dingfang Bu, Xuejun Zhu,
KeWei Wang,
Ruoyu Li,
Yong Yang
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ABSTRACT: Olmsted syndrome (OS) is a rare congenital disorder characterized by palmoplantar and periorificial keratoderma, alopecia in most cases, and severe itching. The genetic basis for OS remained unidentified. Using whole-exome sequencing of case-parents trios, we have identified a de novo missense mutation in TRPV3 that produces p.Gly573Ser in an individual with OS. Nucleotide sequencing of five additional affected individuals also revealed missense mutations in TRPV3 (which produced p.Gly573Ser in three cases and p.Gly573Cys and p.Trp692Gly in one case each). Encoding a transient receptor potential vanilloid-3 cation channel, TRPV3 is primarily expressed in the skin, hair follicles, brain, and spinal cord. In transfected HEK293 cells expressing TRPV3 mutants, much larger inward currents were recorded, probably because of the constitutive opening of the mutants. These gain-of-function mutations might lead to elevated apoptosis of keratinocytes and consequent skin hyperkeratosis in the affected individuals. Our findings suggest that TRPV3 plays essential roles in skin keratinization, hair growth, and possibly itching sensation in humans and selectively targeting TRPV3 could provide therapeutic potential for keratinization or itching-related skin disorders.
The American Journal of Human Genetics 03/3012; 90(3):558-64. · 10.60 Impact Factor
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Zhimiao Lin,
Quan Chen,
Lei Shi,
Mingyang Lee,
Kathrin A Giehl,
Zhanli Tang,
Huijun Wang,
Jie Zhang,
Jinghua Yin,
Lingshen Wu,
Ruo Xiao,
Xuanzhu Liu,
Lanlan Dai, Xuejun Zhu,
Ruoyu Li,
Regina C Betz,
Xue Zhang,
Yong Yang
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ABSTRACT: Pure hair and nail ectodermal dysplasia (PHNED) is a congenital condition characterized by hypotrichosis and nail dystrophy. Autosomal-recessive PHNED has previously been mapped to chromosomal region 12q12-q14.1, which contains the type II hair keratin and HOXC clusters. Hoxc13-null mice are known to develop hair and nail defects very similar to those seen in human PHNED. We performed whole-exome sequencing in a consanguineous Chinese family affected by PHNED and identified a homozygous nonsense mutation (c.390C>A [p.Tyr130(∗)]) in HOXC13 in all affected individuals. In an additional affected female from a consanguineous Afghan family, we found a 27.6 kb homozygous microdeletion involving the first exon of HOXC13. We examined HOXC13 expression in scalp specimen obtained from the index individual of the Chinese family and detected dramatically reduced mRNA levels in skin tissue and nearly absent protein staining in hair follicles, suggesting a mechanism of nonsense-mediated mRNA decay. We also observed markedly decreased expression of four HOXC13 target genes in the specimen. Taken together, our results demonstrate that loss-of-function mutations in HOXC13 cause autosomal-recessive PHNED and further highlight the importance of HOXC13 in hair and nail development.
The American Journal of Human Genetics 10/2012; · 10.60 Impact Factor
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ABSTRACT: Castleman's disease (CD) is an uncommon entity characterized by a massive growth of lymphoid tissue. There are two types: the hyaline-vascular (HV) type and the plasma cell (PC) type. The purpose of this study was to evaluate the clinical value of multiple detector computed tomography (MDCT) in the diagnosis and planning of treatment for hyaline-vascular CD.
Fifty-two cases of confirmed hyaline-vascular CD were retrospectively reviewed. Unenhanced and contrast-enhanced MDCT scans had been performed in all patients, followed by surgery and pathological analysis of the lesion. Original MDCT transverse and reconstructed images were used for image interpretation. Features of the lesion and its adjacent structures were identified.
The lesion was present in the thorax of 24 patients and the abdomen in 28. Obvious features of hyaline-vascular CD (especially feeding vessels and draining veins) and its adjacent structures were demonstrated on 52 patients.
On MDCT imaging, original MDCT transverse and reconstructed images provide an excellent tool for diagnosis of hyaline-vascular CD and have high value in the determination of a treatment plan.
European journal of radiology 06/2011; 81(9):2436-9. · 2.65 Impact Factor
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ABSTRACT: This phase IIa study aimed to study the efficacy and safety of hemoporfin in photodynamic therapy (PDT) with a 532 nm continuous laser for port-wine stain (PWS).
In this 8-week open-labeled study in three centers, three different laser exposure times (532 nm continuous laser for 20, 30 and 40 min) were used in stage I, group A, stage II, group B and stage III, group C, respectively. Primary efficacy assessment was performed by an independent group of experts, who reviewed the standardized photos. Secondary efficacy assessment consisted of the subjective grading of the PWS fading by the investigators and the patients. Treatment reactions and adverse events (AE) were recorded separately.
Forty patients were initially enrolled in the study, but stage III had to be cancelled eventually for the safety of the patients. Patients in groups A and B showed similar satisfactory results in efficacy assessments, the total 'response' rate being 80.0% and 94.7% in groups A and B, respectively. The AE rates were also similar in the two groups. Self-limiting photosensitive dermatitis and hyperpigmentation were the most frequently observed AE.
Hemoporfin-PDT is effective and safe for patients with PWS aged 16-50.
Photodermatology Photoimmunology and Photomedicine 02/2011; 27(1):17-23. · 1.30 Impact Factor
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ABSTRACT: This is the first well-controlled study of the use of botulinum toxin type A (BoNTA) for glabellar lines in China.
To evaluate the safety and efficacy of BoNTA in the treatment of glabellar lines in Chinese subjects.
A total of 227 subjects received a single treatment in a 3:1 randomization ratio of BoNTA (20 U):placebo and were observed for 120 days after injection. Effective outcome measures included investigator's rating of wrinkle severity at maximum frown and rest and subjects' global assessment and self-perception of age.
A significantly higher responder rate at maximum frown, ranging from 94.1% at day 30 to 52.9% at day 120, was noted in the BoNTA group. The proportion of subjects with none or mild glabellar lines at rest was 66.7% in the BoNTA group at day 30. Most (95.3%) of the subjects treated with BoNTA reported better than 50% improvement at day 30, and self-perception of age was less than chronological age. There were no statistically significant differences in adverse events reported between the two groups (p=.06).
A single treatment of 20 U of BoNTA was effective and safe in reducing glabellar lines in Chinese subjects.
Dermatologic Surgery 12/2009; 36(1):102-8. · 1.80 Impact Factor
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ABSTRACT: Hartnup disease is a rare autosomal-recessive abnormality of renal and gastrointestinal neutral amino acid transport associated with neurologic, psychiatric, and dermatologic symptoms. Mutations in the SLC6A19 gene have been proposed to be responsible for the underlying changes in this disorder.
To investigate a pedigree with Hartnup disorder and to search for the mutation in the SLC6A19 gene in this pedigree.
The encoding exons of the SLC6A19 gene were amplified and sequenced from genomic DNA samples. Amino acids were determined in urine samples from the proband and her family members.
The proband and her brother had a homozygous mutation of c.850G > A in the SLC6A19 gene, causing G284R in the transmembrane domain of the SLC6A19 transporter, inherited from their parents who were heterozygous carriers. Their urine samples showed increased values of eight neutral amino acids.
We found a novel homozygous mutation of G284R in the transmembrane domain of the SLC6A19 transporter in the proband, with typical dermatologic and neurologic manifestations and increased levels of urinary neutral amino acids.
International journal of dermatology 05/2009; 48(4):388-92. · 1.18 Impact Factor
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ABSTRACT: Paraneoplastic pemphigus patients (PNP) develop a group of autoantibodies, among which those against envoplakin and periplakin are almost always found. Epitope mapping has indicated that the linker subdomains of the proteins harbor the major antigenic sites recognized by PNP sera. In order to detect specific autoantibodies for the diagnosis of PNP, we expressed recombinant proteins containing linker subdomains of human periplakin and envoplakin in a human kidney cell line, and used them as the antigens for ELISAs. We found that all of the sera from 16 PNP patients recognized these two recombinant proteins by ELISA, and sera from 20 pemphigus vulgaris (PV), 12 pemphigus foliaceus (PF), 20 bullous pemphigoid (BP), 2 Castleman's tumor without PNP and 20 normal controls showed negative results. We also expressed the extracellular domain of desmoglein 3 (Dsg3) in the cell line, and used this recombinant Dsg3 as the ELISA antigen. Only 11 of our 16 PNP sera were positive, and most PV sera were positive. Our findings indicate that ELISAs using the recombinant proteins containing linker subdomains of envoplakin and periplakin expressed in a human cell line as the antigens are highly sensitive and specific for the diagnosis of PNP.
Archives for Dermatological Research 10/2008; 301(10):703-9. · 2.28 Impact Factor
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ABSTRACT: We have studied the role of lymphoproliferative tumors in the pathogenesis of autoimmune and the origin of the autoantibodies in PNP. Objectives of this study is to understand the characteristics of immunoglobulin genes of the B-cells isolated from the tumor which can produce auto-antibody.
Total RNA of the tumor cells was then isolated and the mRNA was reversely transcribed into cDNA. V(H) and V(L) genes were amplified and cloned and their sequences were analyzed.
49 V(H) genes (527 to 577 bp) and 36 V(L) genes (445 to 454 bp) sequences were cloned from five tumors. All of the IgV(L) were mostly homologous to IGKV4-01 germ-line gene. The frequency of IgV(H) germ-line gene usage in a decreasing order was IGHV3-23 > IGHV3-9 > IGHV4-31 > IGHV4-59. There was more nucleotide changes occurred in complementary determining regions (CDR) than those in the framework regions (FR) in the V(H) and V(L) of B cell clones. In both V(H) and V(L), the probability (P) that the number of observed replacement mutations (R) in the CDRs would occur by random chance was low.
The clones of B-lymphocytes in the tumors carrying possibly functional rearranged immunoglobulin heavy and light chain genes were isolated and there were high incidences of somatic mutations in CDRs and relatively conserved sequences in framework region.
International Journal of Dermatology 11/2007; 46(11):1146-54. · 1.14 Impact Factor
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ABSTRACT: Paraneoplastic pemphigus (PNP) is a life-threatening autoimmune blistering skin disease. Clinically, it is characterized by severe mucosal erosions and various cutaneous lesions associated with lymphoproliferative neoplasmas. Suprabasal acantholysis and clefts with scattered necrotic keratinocytes are the unique histopathological features. PNP patient sera recognize multiple antigens, which have been identified as the plakin protein family that includes desmoplakin, bullous pemphigoid antigen I (BPAG1), envoplakin and periplakin, and desmogleins 1 and 3. Castleman's tumor, non-Hodgkin's lymphoma, thymoma, follicular dendritic cell sarcoma and chronic lymphocytic leukemia are the commonly associated neoplasmas in PNP. We have also demonstrated that the autoantibodies reacting to epidermal proteins are directly produced by the cells in the associated tumors. Bronchiolitis obliterans is frequently found in PNP and may cause respiratory failure and death. In our experience, the early detection and removal of the tumor and i.v. administration of immunoglobulin are critical for the treatment of PNP.
The Journal of Dermatology 09/2007; 34(8):503-11. · 1.49 Impact Factor
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Journal of Dermatological Science 07/2007; 46(3):211-3. · 3.72 Impact Factor
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ABSTRACT: Lipoid proteinosis is caused by loss-of-function mutations in the glycoprotein extracellular matrix protein 1 (ECM1). We report here mutation analysis of the ECM1 gene in a Chinese family with lipoid proteinosis. A 10-year-old boy presented with a hoarse voice, acneiform scars and yellow skin nodules, as well as beaded eyelid papules and a thickened sublingual frenulum. Skin biopsy showed widespread deposition of hyaline material in the dermis and thickened basement membrane. His elder sister had the same clinical manifestations. The coding region of ECM1 was amplified and sequenced and both affected siblings were shown to have a novel homozygous single nucleotide substitution, c.658T>G, in exon 6, which converts cysteine to glycine, designated p.C220G. Both parents were heterozygous for this mutation which was not detected in 100 control chromosomes. Missense mutations in the ECM1 gene are an unusual finding in lipoid proteinosis, but this case adds to the spectrum of disease-associated mutations in this rare genodermatosis.
Acta Dermato Venereologica 01/2007; 87(5):387-9. · 3.18 Impact Factor
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ABSTRACT: To obtain potential skin whitening agents from traditional Chinese herbs, we tested changes of melanin content in melanocyte cell lines after treatment with extracts of 90 traditional Chinese herbs.
Mouse melanocyte cell lines were used. Depigmentation activity of the herb extracts were first screened in Mel-Ab cells, and then re-evaluated in melan-a cells and co-culture of melan-a and SP-1 cells. Melanin content and cell viability were the two indications for evaluation. Tyrosinase activity and the expression of melanin synthesis related enzymes in cells treated with the herb extracts were also tested.
Nine herb extracts were proved to have depigmentation activity similar to or better than that of arbutin and low cytotoxicity to melanocytes. Two of them were more effective in co-cultured melan-a cells. Most of the effective herb extracts inhibited tyrosinase activity and the expression of tyrosinase. Some of them also inhibited tyrosinase related protein-1 and/or tyrosinase related protein-2 in cultured cells.
We have found 9 herb extracts to be promising skin whitening agents. Among them, water extract of Galla Chinensis and ethanol extract of Radix Clematidis exhibited higher depigmentation activity and caused lower tyrosinase activity in cell culture assays and are worthy to be further studied.
Biological & Pharmaceutical Bulletin 10/2006; 29(9):1947-51. · 1.66 Impact Factor
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ABSTRACT: Sera from paraneoplastic pemphigus (PNP) immunoprecipitate multiple antigens from human epidermal protein extract. In this study, we further characterized the autoantibodies in 12 PNP sera. Immunoblotting using recombinant linker subdomains of envoplakin, periplakin, desmoplakin, and bullous pemphigoid antigen I found that 11 of the 12 sera recognized linker subdomains of envoplakin and periplakin. We then synthesized 12 peptides covering the linker subdomain of envoplakin for ELISA. One of the peptides, peptide no. 8, was recognized by nine out of the 12 sera with a higher affinity. A method of ligand-receptor binding assay was designed and performed using this peptide labeled with fluorescence as the ligand. Peptide no. 8 bound to CD20+ cells in Castleman's tumors from the patients whose sera were positive to this peptide by ELISA. Our data suggest that the linker subdomain of plakin proteins may be one of the major areas recognized by PNP autoantibodies, and epitopes in the linker subdomain of envoplakin recognized by PNP autoantibodies with a high affinity are dispersed in several areas and are variable among PNP patients. We also demonstrate that B-lymphocyte clones specifically reacting to epidermal proteins exist in Castleman's tumors from PNP.
Journal of Investigative Dermatology 04/2006; 126(4):832-40. · 6.31 Impact Factor
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Jing Wang, Xuejun Zhu,
Ruoyu Li,
Ping Tu,
Rengui Wang,
Lanbo Zhang,
Ting Li,
Xixue Chen,
Aiping Wang,
Shuxia Yang,
Yan Wu,
Haizhen Yang,
Suzhen Ji
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ABSTRACT: Castleman tumor, a rare lymphoproliferative disorder, is one of the associated tumors in paraneoplastic pemphigus. We analyzed the characteristics of a group of patients with Castleman tumor to clearly understand and to improve the prognosis of the disease.
Ten cases of paraneoplastic pemphigus associated with Castleman tumor treated in the Department of Dermatology, Peking University First Hospital, Beijing, China, from May 1, 1999, to March 31, 2004, were analyzed for clinical aspects, characteristics and histologic features of the tumors, and computed tomographic findings. Literature was reviewed and data were compared with our cases. Castleman tumor was a frequently reported neoplasm in association with paraneoplastic pemphigus in China. The disease was found to be caused by an autoimmune reaction originating from the B lymphocytes in the Castleman tumor.
Castleman tumor in association with paraneoplastic pemphigus is a commonly reported subtype of paraneoplastic pemphigus in China. Early detection and removal of the Castleman tumor are crucial for the treatment of this tumor-associated autoimmune disease.
Archives of Dermatology 11/2005; 141(10):1285-93. · 3.89 Impact Factor
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ABSTRACT: Our understanding of the role of B-cells in the immunopathogenesis of certain antibody mediated diseases has developed remarkably in the past few years. In this review, autoantibody mediated immune disorders associated with pathogenic B-cell clones are discussed. We have focused on the roles and pathogenic mechanisms of B-cell clones in autoantibodyimmune diseases. The roles of pathogenic B-cells in Castleman's disease in PNP patients is used as one example. The developments in the treatment of B-cell mediated autoimmune diseases, such as intravenous immunoglobulin (IVIg), targets the regulatory pathway of B-cells, using anti-CD20, CD19, CD22 and, CD95 monoclonal antibody therapy, etc. are also discussed. Immunotherapy, targeting specific pathogenic B-cells, is believed to be one approach in the management of autoimmune diseases.
Journal of Dermatological Science 01/2005; 36(3):141-8. · 3.72 Impact Factor
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ABSTRACT: Paraneoplastic pemphigus is an autoimmune mucocutaneous disease associated with Castleman's tumours, which when surgically removed often result in great improvement of mucocutaneous lesions. An IgG autoantibody against epidermal proteins is often used as a diagnostic marker for disease. Our aim was to ascertain the role of Castleman's tumours in production of the autoantibody and pathogenesis of paraneoplastic pemphigus.
We enrolled seven patients with paraneoplastic pemphigus associated with Castleman's disease and assessed the effect of removal of tumours on mucocutaneous lesions in six individuals and on autoantibody titre with indirect immunofluorescence in four patients. We cultured tumour cells from one patient and assayed the secreted autoantibody. Finally, we characterised the gene sequence and expression of the variable region of the immunoglobulin heavy chain (IgV(H)) in tumour B cells from all patients by reverse transcription-PCR, DNA sequencing, and in-situ hybridisation.
Cutaneous lesions disappeared within 6-11 weeks after resection of tumours. Mucosal lesions also improved in this period, but lasted for 5-10 months overall. Autoantibody titre decreased and became undetectable within 5-9 weeks in three of four patients assessed. We identified secreted autoantibody, similar to that identified in patients' serum, in cultured tumour cells. The tumour B-cells of the seven patients shared and expressed two rearrangement patterns of complementarity determining region 3 (CDR3) of IgV(H).
Secreted autoantibody from Castleman's tumours, which reacts against epidermal proteins, could be an essential factor in the pathogenesis of paraneoplastic pemphigus. We noted clonal rearrangement, resulting in similar variable regions of IgV(H), in tumour B cells isolated from all seven patients. However, whether this pattern is associated with autoimmunity remains to be ascertained.
The Lancet 03/2004; 363(9408):525-31. · 38.28 Impact Factor
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ABSTRACT: To clone and express xeroderma pigmentosum, complementation group A (XPA) cDNA and to identify its recombinant protein.
Coding region of XPA cDNA was amplified from human tonsil cDNA by reverse transcription and nested PCR. The PCR product was cloned into pBluescript vector, confirmed by DNA sequencing, cloned in frame into a prokaryotic expression vector pTrcHis C and expressed in E. coli. TOP10. The recombinant fusion protein was identified by immunoblotting.
The entire coding region of XPA cDNA was cloned and expressed. The fusion XPA protein was identified by anti-XPA monoclonal antibody on western blot.
Cloning of human XPA cDNA and successful expression of recombinant XPA protein will be useful for the construction of a viral gene transfer vector for the gene therapy of XPA.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 09/2003; 35(4):426-8.
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ABSTRACT: To screen and identify gene mutations of 11 Chinese patients with Hailey-Hailey disease (HHD).
Cases of HHD were diagnosed by history, clinical menifestations and pathology. Then genomic DNA samples of patients were extracted from perpheral blood leukocytes, and polymerase chain reaction(PCR), DNA sequencing were performed.
We found five mutations in ATP2C1 gene including 3 nonsense mutations and 2 splicing mutations. Four of them were novel mutations.
Both nonsense mutation and splicing mutation could affect the rusult of transcription, translation, and the functions of protein encoded by ATP2C1 gene, so the mutations reported in this study is the underlying cause of HHD.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 09/2003; 35(4):390-3.
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ABSTRACT: Ureaplasma urealyticum is a causative agent of non-gonococcal urethritis and is implicated in the pathogenesis of several other diseases. However, U. urealyticum is also frequently found in the normal genitourinary tract. To characterize the distribution pattern of biovars and genotypes in normal physical check-up women and in sex workers, cervical swabs taken from 261 physical check-up clients and 98 sex workers were cultured. Positive cultures were further biotyped and genotyped by PCR. The data indicate that a) U. urealyticum is more frequently isolated in sex workers than in physical check-up women (p < 0.001); b) infection with only one genotype (genotype 1, 3 or 6) of biovar 1 is frequently found in physical check-up women; c) biovar 2 infection and mixed infection caused by more than one genotype of biovar 1 are more prevalent in sex workers than in physical check-up women (p < 0.001 and p < 0.01, respectively); d) no difference in distribution of genotype 1, 3 and 6 of biovar 1 is found between sex workers and physical check-up women (p = 0.396); e) the PCR method described here is relatively simple, rapid and specific for the biotyping between biovar 1 and 2 and genotyping of genotypes 1, 3, 6, and 14 in biovar 1.
Acta Dermato Venereologica 01/2003; 83(3):175-8. · 3.18 Impact Factor
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ABSTRACT: We describe a Chinese family with generalized atrophic benign epidermolysis bullosa (GABEB), a non-lethal variant of junctional epidermolysis bullosa. The proband was an offspring of consanguineous parents, had generalized blisters since birth and developed severe alopecia during early childhood. Ultrastructural examination of the proband's skin revealed fissures in the lamina lucida. Immunofluorescence assays using a monoclonal antibody recognizing the extracellular domain of the 180 kDa bullous pemphigoid antigen (BPAG2) showed loss of fluorescent signal in the basal membrane zone of the skin. DNA sequencing revealed a homozygous C-to-G transversion at nucleotide position 899 in exon 11 of the COL17A1 gene, which encodes BPAG2. This mutation results in serine to cysteine at position 265, which is located in a highly conserved region of the intracellular domain of BPAG2. We showed that the proband's father was heterozygous for this mutation. In addition, we found a novel polymorphic substitution of C-to-G at nucleotide position 798 in exon 10 of the COL17A1 gene, which results in an I233M change in BPAG2 and is a common polymorphic allele in a limited Chinese population.
Journal of Dermatological Science 05/2002; 28(3):181-6. · 3.72 Impact Factor
