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Background Ichthyosis vulgaris (IV; OMIM 146700) is a very common inherited skin disorder. Loss-of-function mutations in the filaggrin gene ( FLG) have been identified as the cause of IV. In a previous study, we found that the percentage of FLG null mutations was lower in IV associated with atopic dermatitis (AD) than in IV not associated with AD (isolated IV). We speculated that some clinical manifestations of IV in patients with AD are not induced by FLG mutations. Objectives In order to clarify this issue, we collected 21 IV pedigrees, 33 patients with sporadic isolated IV and 116 patients with AD-associated IV to analyse FLG mutation frequency and filaggrin expression in isolated IV and AD-associated IV. Methods A comprehensive sequencing of the FLG gene in all patients was performed using an overlapping polymerase chain reaction (PCR) strategy. We also studied the immunohistochemistry of profilaggrin/filaggrin protein expression in the skin and measured the mRNA expression using real-time PCR in seven patients, including one patient with IV harbouring the mutation c.3321delA, two patients with AD-associated IV harbouring c.3321delA and c.6834del5, and four patients with AD-associated IV without FLG mutations. Results The percentage of mutations in the FLG gene was 74% and 43% in patients with isolated IV and patients with AD-associated IV, respectively. Immunohistochemical staining revealed that profilaggrin/filaggrin peptides were remarkably reduced in the epidermis of all the patients. All the patients with either AD or IV showed lower FLG mRNA expression compared with the normal control. Conclusions These results indicate that factors other than FLG gene mutations can downregulate profilaggrin/filaggrin expression, leading to the ichthyosiform phenotype in the context of AD. [ABSTRACT FROM AUTHOR]

Aims: Daptomycin, one of the A21978C factors produced by Streptomyces roseosporus, is an acidic cyclic lipopeptide antibiotic with potent activity against a variety of Gram-positive pathogens. To increase the titre of this extensively used and clinically important antibiotic, we applied a reported-guided rpsL mutation selection system to generate strains producing high levels of A21978C. Methods and Results: In the reporter design, dptE was chosen as the overexpressing target, and neo-encoding neomycin phosphotransferase as the reporter. Using this reporter-guided selection system, 20% of the selected, streptomycin-resistant mutants produced greater amounts of A21978C than the starting strain. The selection system increased the screening efficiency about 10-fold with a frequency of 1·7% A21978C overproducing strains among str r mutants. A21978C production was increased approximately 2·2-fold in the rpsL K43N mutant. Conclusions: The combination of ribosome engineering and reporter-guided mutant selection generated an A21978C overproducing strain that produced about twice as much A21978C as the parental strain. Significance and Impact of the Study: The strategies presented here, which integrated the advantages of both ribosome engineering and reporter-guided mutation selection, could be applied to other bacteria to improve their yield of secondary metabolites. [ABSTRACT FROM AUTHOR]

SUMMARY The prognosis of esophageal squamous cell carcinoma (ESCC) is poor. It is urgent to improve this situation. Epidermal growth factor receptor (EGFR)-targeted therapy possesses a promising clinical efficacy. Mutations of EGFR and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) have been identified in esophageal carcinoma, but corresponding Chinese data are limited. So we investigated the mutation status of EGFR and KRAS in Chinese patients with ESCC, and explored their correlations with clinicopathological features. Formalin-fixed paraffin-embedded surgically resected tumor samples were obtained from 50 randomly selected Chinese patients with ESCC. EGFR mutations in exons 18-21 were detected by Scorpions amplification refractory mutation system technology. KRAS mutations in codons 12, 13 were detected by direct sequencing of polymerase chain reaction products. The correlations between clinicopathological features and the mutation status of EGFR and KRAS were analyzed using the Statistical Package for the Social Sciences. In the present study, EGFR mutations were found in 7 (14%) out of 50 patients, including G719X missense mutation ( n= 1), in-frame deletion ( n= 2), and L858R missense mutation ( n= 5). Six (12%) out of 50 patients had KRAS mutations in codon 12. Concurrent EGFR and KRAS mutations were detected in one sample. The presences of EGFR and KRAS mutations were not associated with gender, age, smoking history, cell differentiation, or cancer stage. In conclusion, the incidence of EGFR mutations in Chinese patients with ESCC was higher than that of previous reports, and the incidence of KRAS mutations was not low. EGFR and KRAS mutations were mainly located in exons 19 and 21 and codon 12, respectively. Unlike in NSCLC, concurrent EGFR and KRAS mutations existed. [ABSTRACT FROM AUTHOR]

Darier disease (DD) is a rare autosomal dominant skin disorder with characteristic abnormal keratinization and acantholysis. The causative gene, ATP2A2, is located on chromosome 12, and encodes a sarco/endoplasmic reticulum calcium pump ATPase (SERCA2). Two Chinese patients with sporadic DD participated in this study. Genomic sequence analysis identified two novel missense mutations (c.742C>A and c.2098A>G) in the ATP2A2 gene. Our findings provide an additional ATP2A2 mutation causative for DD development, and new lines of evidences for the understanding of genotype-phenotype correlations. [ABSTRACT FROM AUTHOR]

The article discusses the medical condition of Chinese families with autosomal dominant disorder Hailey-Hailey disease (HHD) caused by mutations in adenosine triphosphatase (ATPase), Ca++ transporting, type 2C, member 1 (ATP2C1) gene. It discusses the linkage between HHD cases and condyloma acuminata (CA) in two Chinese families and its effect on the human secretory pathway Ca2+/ Mn2 ± ATPase protein 1. It also presents three missense mutations in the ATP2C1 gene.