Da Lin

The genetic epidemiology of alopecia areata in China.

Background  Alopecia areata (AA) is hypothesized to be an organ‐specific autoimmune disease with genetic predisposition and an environmental trigger. There are few clinical data in Asians.

Genetic heterogeneity in acrokeratosis verruciformis of Hopf.

Background.  Acrokeratosis verruciformis of Hopf (AKV) is a rare genodermatosis characterized by multiple flat‐topped, flesh‐coloured papules on the dorsa of hands and feet, and punctuate keratoses on the palms and soles. A mutation in the ATP2A2 gene has been shown to be associated with AKV and with Dariers disease (DD).

Knockdown of EIF3D suppresses proliferation of human melanoma cells through G2/M phase arrest

Skin cancer is the most common malignancy with increasing incidence rates worldwide. The advanced form of skin cancer, melanoma, is resistant to conventional treatment methods, which motivated researchers to identify an alternative effective therapeutic approach. This study was designed to identify the effects of small interfering RNA (si‐RNA) mediated silencing of eukaryotic translation initiation factor 3, subunit D (EIF3D) against melanoma cell survival. Briefly, a lentivirus‐mediated RNA interference system was employed to knock down EIF3D expression in A375 and A431 melanoma cells. The cell proliferation was analyzed by methylthiazoletetrazolium (MTT) and colony formation assays. The cell cycle progression was investigated using flow cytometry. Results revealed that si‐RNA–mediated knockdown of EIF3D significantly reduced the gene and protein expression levels of EIF3D in melanoma cells. Furthermore, knockdown of EIF3D led to a significant reduction in cell proliferation due to G2/M phase cell cycle arrest. Apparently, the study demonstrated the critical involvement of EIF3D in the survival and progression of melanoma cells and depletion of EIF3D could be developed as a possible therapeutic option in the gene‐targeted treatment of melanoma.

Exome sequencing identifies SLC17A9 pathogenic gene in two Chinese pedigrees with disseminated superficial actinic porokeratosis

Background Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant genodermatosis characterised by annular lesions that has an atrophic centre and a prominent peripheral ridge distributed on sun exposed area. It exhibits high heterogeneity, and five linkage loci have been reported. The mevalonate kinase (MVK) gene located on 12q24 has been confirmed as one of the disease-causing genes. But, the pathogenesis of a large part of DSAP remains unclear so far. Methods The recruited with DSAP carried no MVK coding mutations. Exome sequencing was performed in two affected and one unaffected individual in Family 1. Cosegregation of the candidate variants was tested in other family members. Sanger sequencing in 33 individuals with familial DSAP and 19 sporadic DSAP individuals was performed for validating the causative gene. Results An average of 1.35×105 variants were generated from exome data and 133 novel NS/SS/indels were identified as being shared by two affected individuals but absent in the unaffected individual. After functional prediction, 25 possible deleterious variants were identified. In Family 1, a missense variant c.932G>A (p.Arg311Gln) in exon 10 of SLC17A9 was observed in cosegregation with the phenotype; this amino acid substitution was located in a highly conserved major facilitator superfamily (MFS) domain in multiple mammalian. One additional missense variant c.25C>T (p.Arg9Cys) in exon 2 of SLC17A9 was found in Family 2. Conclusions The result identified SLC17A9 as another pathogenic gene for DSAP, which suggests a correlation between the aberrant vesicular nucleotide transporter and the pathogenesis of DSAP.

A novel missense mutation of the ATP2A2 gene in a Chinese family with Darier’s disease

Darier’s disease (DD) is an autosomal dominant skin disorder that is characterized by multiple keratotic papules, focal loss of adhesion and abnormal keratinization. Mutations in the ATP2A2 gene encoding sarco/endoplasmic reticulum calcium pumping ATPase type 2 have been identified as the molecular basis of DD. We report here a three-generation family with DD, and examined ATP2A2 gene mutations in this family by direct sequencing. A novel missense mutation A→G was identified in exon 12, nucleotide 1704, which leads to the substitution of lysine by arginine at codon 514 (K514R). This study contributes to the database on ATP2A2 in DD, and further illustrates the extensive diversity of mutational events that lead to the different phenotypes of DD.

A novel KIT missense mutation in one Chinese family with piebaldism.

Piebaldism is an autosomal dominant disorder characterized by congenital leukoderma, mostly affecting forehead, abdomen and knee. Previous studies have revealed that piebaldism is caused by mutations of the KIT gene, which encodes the cell surface transmembrane tyrosine kinase receptor for KIT ligand. We reported here a Chinese Han family with piebaldism, and performed mutation detection of KIT gene by direct sequencing. A novel missense mutation C58G was identified in the patients, but not in the healthy individuals from the family and 100 unrelated controls. This study contributes to the database on KIT in piebaldism and enriches the knowledge about the genotype/phenotype correlation.

A novel GJB3 (Cx31) missense mutation in a Chinese patient with erythrokeratodermia variabilis.

remover for several years without any problem suggests that the laboratory had used another cocamidopropylbetainamide MEA chlorure, perhaps provided by a new supplier. Although DMAPA is present in very small quantities in the final CAPB product, the possibility that additional surfactant may act as a sensitizer should be considered, especially on the very thin skin of the eyelids. Further to a declaration to the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS), the laboratory recalled the incriminated batch. These observations provide further evidence that CAPB patch tests are not efficient enough to detect contact allergy to commercial CAPB, containing DMAPA as impurity. These cases also point out that we should suspect cosmetics even if they were used ‘safely’ for a long time, in case of a change in the supplier of ingredients.

A case of acrokeratoelastoidosis

Acrokeratoelastoidosis (AKE) is a rare skin disorder characterized by multiple, small, flat-topped, keratotic papules and plaques distributed predominantly on the margins of the hands and feet, sometimes extending to the dorsal and palmar–plantar surfaces. Approximately 40 cases have been reported since Costa described the first case of AKE in 1953. The most common histological features of AKE are hyperkeratosis of the epidermis, mild acanthosis, and both a decrease in number and a decrease in fragmentation of elastic fibres within the dermis. We report a woman with distinct clinical and histological features of AKE. A 30-year-old Chinese woman presented with a 10year history of multiple wart-like lesions, which had gradually increased over the years without any itching or pain. Neither her parents nor children had any similar condition. On physical examination, a number of round, skincoloured, flat-topped, hyperkeratotic papules, 2–4 mm in diameter, were observed on the dorsa of both hands and both wrists. These papules were grouped or dispersed, and had a lustreless surface. A small portion of papules coalesced into plaques. In addition, multiple pinpoint-sized to 1 mm glossy papules were also seen on the dorsal aspects of her wrists as well as the back of her feet. Many yellow white translucent papules 1–2 mm in diameter were diffusely distributed over her palms (Fig. 1a–c). There was no involvement of her nails, and her general health was good.

Knockdown of myosin VI by lentivirus-mediated short hairpin RNA suppresses proliferation of melanoma.

Myosin VI has been reported to be associated with the progression of ovarian and prostate cancer. The aim of the present study was to reveal the role of myosin VI in the proliferation of melanoma. Briefly, lentivirus‑mediated short hairpin RNA (shRNA) was designed specifically to silence myosin VI in A375 and A431 cell lines. Expression levels of myosin VI were then analyzed in the two cell lines by quantitative polymerase chain reaction and western blot analyses. Cell viability was assessed using MTT and colony formation assays. In addition, the cell cycle distribution was determined by flow cytometry. The results demonstrated that knockdown of myosin VI significantly suppressed melanoma cell viability and proliferation, and induced cell cycle arrest in G0/G1 phase. To the best of our knowledge, the present study was the first to assess the role of myosin VI in the growth of melanoma. Knowledge of the underlying mechanism of the role myosin VI in skin cancer cells may aid in the development of novel methods of melanoma diagnosis and therapy in the future.