Xi'an Fu

Investigation of 20 non-HLA (human leucocyte antigen) psoriasis susceptibility loci in Chinese patients with psoriatic arthritis and psoriasis vulgaris.

Background  Recently, a number of non‐HLA (human leucocyte antigen) psoriasis genetic susceptibility loci have been identified through genome‐wide association studies, but data on their association with psoriatic arthritis (PsA) are lacking.

CARD9 mutation linked to Corynespora cassiicola infection in a Chinese patient.

Corynespora cassiicola is a plant pathogen associated with leaf‐spotting disease. The fungus has been found on diverse substrates: leaves, stems and roots of plants; nematode cysts and human skin. It rarely causes human infections. Here we report one case of subcutaneous phaeohyphomycosis caused by C. cassiicola with prominent tissue necrosis in a woman. All of her clinical features pointed towards a genetic linkage. Hence, whole‐exome sequencing and Sanger sequencing were performed on this patient. One mutation of CARD9 was detected.

Identification of three novel frameshift mutations of the MVK gene in four Chinese families with disseminated superficial actinic porokeratosis

MADAM, Porokeratosis is a group of hereditary disorders of epidermal keratinization, characterized by keratotic lesions with an atrophic centre and a prominent peripheral ridge, and a typical histological cornoid lamella. There are several clinical subtypes of porokeratosis, including disseminated superficial actinic porokeratosis (DSAP), disseminated superficial porokeratosis (DSP), classic porokeratosis of Mibelli (PM), porokeratosis palmar, plantar and disseminated, and linear porokeratosis (LP), all of which show typical pathological manifestations, i.e. cornoid lamella in the epidermis. Among these, DSAP is the most common clinical subtype of porokeratosis, and has been widely studied to identify the genetic variance. To date, four genetic loci have been mapped to be responsible for DSAP: 12q23.2-24.1 (DSAP1), 15q25.1-26.1 (DSAP2), 1p31.3-p31.1 (DSAP3) and 16q24.1-24.3 (DSAP4). The SSH1 and SART3 genes located in DSAP1 have been identified as the causal genes in two Chinese families, respectively. Recently, Zhang’s group performed exome sequencing in one family with DSAP and identified several mutations of the MVK gene in 33% of familial DSAP and 16% of sporadic cases. In this study, we conducted direct DNA sequencing of MVK, SSH1 and SART3 to investigate the causal variance in 10 families with DSAP and four sporadic cases. All the cases recruited manifested the multiple, small, annular, anhidrotic, keratotic lesions predominantly in sun-exposed areas of the skin (Fig. 1a). The lesions began to develop in adolescence with near complete penetrance by the third to fourth decades of life. Sunlight exposure to ultraviolet radiation can aggravate the lesions. All the clinical and histological characteristics of the cases supported the clinical diagnosis of DSAP. However, in the proband of family 2 and sporadic case 1, in addition to the typical manifestations of DSAP, there were also verrucous plaques in left gluteal region and thigh (Fig. 1b). Informed consent of the patients and approval from the human medical and ethics committee of Shandong Provincial Institute of Dermatology and Venereology were obtained. Genomic DNA was extracted from the peripheral blood of 14 affected individuals and two unaffected individuals from 10 families with DSAP, four sporadic cases and 100 healthy controls. All the exons of the MVK, SSH1 and SART3 genes and their flanking intronic sequences of 200 bp were amplified by polymerase chain reaction. After amplification, products were purified and directly sequenced on an ABI 3130xl Genetic Analyser (Applied Biosystems, Foster City, CA, U.S.A.). In total, three frameshift mutations (c.395delT, c.853insA and c.1057delTGGAGGCCACGAAG) of the MVK gene were identified in two families and two sporadic cases (Table 1; Fig. 2). None of these mutations was found in unaffected family members or the 100 controls.

Mutation analysis of the CYLD gene in two Chinese families with multiple familial Trichoepithelioma

Multiple familial trichoepithelioma (MFT) is an autosomal dominant inherited disease characterized by multiple skincoloured papules on the centre of the face. Mutations in the CYLD gene on chromosome 16q12-q13 have been identified as the cause of MFT, and is also responsible for familial cylindromatosis (cylindromas only) and Brooke–Spiegler syndrome (a combination of cylindromas, trichoepitheliomas and spiradenomas). We performed mutation analysis of the CYLD gene in two Chinese MFT families (Fig. 1a) and identified two mutations of the CYLD gene. The patients, whose onset age varied from 20 years to 38 years, were diagnosed based on facial trichoepitheliomas and histopathological findings (Fig. 1b). After informed consent, genomic DNA was extracted from the peripheral blood of family members and 96 healthy controls. Exons of

Lack of association between the single nucleotide polymorphism of ST18 and pemphigus in Chinese population

(5.9%) in the LAMB3 gene are reported as recurrent mutations in Caucasian people, but these are absent in Japanese. p.Arg972* in LAMB3, as in our case, has been previously reported as a recurrent mutation in the worldwide population, but represents only 1.8% of the mutation database. In conclusion, we experienced a Japanese patient with Herlitz junctional EB who initially showed a few blisters on the limited area and identified a novel deletion mutation (c.647delA) in the LAMB3 gene. From his initial clinical features, at first, we suspected him of having dystrophic EB, but it was not until we examined antigen mapping that diagnosis of Herlitz junctional EB was confirmed. Therefore, we would emphasize the importance of antigen mapping study in all cases of EB, even if the initial lesion is mild.

Identification of two novel splice mutations of the ADAR1 gene in two Chinese families with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a rare, autosomal dominant dermatosis, characterized by a mixture of hyperpigmented and hypopigmented macules on the dorsa of the hands and feet. The DSH locus has been mapped to chromosome 1q21, and in 2003, pathogenic mutations were identified in the ADAR1 (adenosine deaminase acting on RNA1) gene. In this study, we performed mutation detection of the ADAR1 gene in two Chinese families with DSH. PCR and direct sequencing of the ADAR1 gene were used to identify and confirm the mutations in the two families. Furthermore, we analysed the RNA transcripts by reverse transcriptase (RT)‐PCR. Two aberrant splice products were confirmed with RT‐PCR and DNA direct sequence analysis. These novel findings further extend our understanding of the role of ADAR1 in DSH.

Analysis of ATP2C1 gene mutations in Chinese patients with Hailey-Hailey disease.

units, accompanied by a smaller decrease in admissions codes as skin diseases. So, part of the answer to the question, What happens to the patients who were previously admitted to dermatology wards when dermatology beds are lost? seems to be that patients previously managed in dermatology wards are instead admitted elsewhere. This may mean that patients are not being cared for as appropriately, so harming their individual care, and also possibly wasting resources through unnecessary investigations, inappropriate treatments and longer admissions. Once a dermatology ward is lost, the associated nursing and medical expertise in inpatient dermatology may be difficult to redevelop. It is important, for the quality of patient care and the prudent use of health-service resources, that the overall issues are considered carefully if reductions in dermatology inpatient facilities are considered. Acknowledgements

Drug resistance in Mycobacterium leprae from patients with leprosy in China.

Previous studies of drug resistance have shown that mutations in the drug resistance‐determining region (DRDR) in the Folp1, RpoB and GyrA genes of Mycobacterium leprae are responsible for resistance to dapsone, rifampin and ofloxacin, respectively.

Glucocorticoid receptor polymorphisms: Lack of association with glucocorticoid resistance among Chinese bullous disease patients.

ciation of psoriasis. We diagnosed the bullae as BP with IgG autoantibodies mainly reactive to LAD-1. IgG autoantibodies to the BP180-NC16a domain were not considered to contribute to form tense bullae essentially, because immunoblotting studies of the BP180-NC16a domain RP showed no positive reactivity. Immunoglobulin G autoantibodies from patients with BP can react to the RP of the BP180-NC16a domain, LAD-1 and/or the BP180 C-terminal domain. In most cases of BP, the BP180-NC16a domain is recognized initially and then the other region as an intramolecular epitope-spreading phenomenon, and BP230 as an intermolecular epitopespreading phenomenon. However, there are cases of BP with autoantibodies only reactive with the outside of the BP180-NC16a domain. We speculated that LAD-1 was initially recognized and the BP180-NC16a domain was secondarily recognized as an unusual inverse direction in this case. Further case series should be accumulated to confirm occurrence of the inverse intramolecular epitope-spreading phenomenon. CONFLICT OF INTEREST: None.

Detection of the STS gene in a family with X-linked recessive ichthyosis.

Sir, X-linked recessive ichthyosis (XLRI, OMIM: 308100) is a genetic disorder of keratinization characterized by dark, adhesive, polygonal, and regular scales of skin. Corneal opacity could also be observed in 1015% of affected individuals.[1] XLRI usually occurred at birth or within 3 months after birth, and affects roughly 1:2000 to 1:6000 males. In 1978, the steroid sulphatase enzyme (STS) deficiency was identified to be responsible for the onset of XLRI.[2] The majority of XLRI patients have complete deletions of the STS gene. Here we performed a mutation analysis of the STS gene in a Chinese XLRI family.