Porokeratosis (PK) is a heterogeneous group of keratinization disorders. No causal genes except MVK have been identified, even though the disease was linked to several genomic loci. Here, we performed massively parallel sequencing and exonic CNV screening of 12 isoprenoid genes in 134 index PK patients (61 familial and 73 sporadic) and identified causal mutations in three novel genes (PMVK, MVD, and FDPS) in addition to MVK in the mevalonate pathway. Allelic expression imbalance (AEI) assays were performed in 13 lesional tissues. At least one mutation in one of the four genes in the mevalonate pathway was found in 60 (98%) familial and 53 (73%) sporadic patients, which suggests that isoprenoid biosynthesis via the mevalonate pathway may play a role in the pathogenesis of PK. Significantly reduced expression of the wild allele was common in lesional tissues due to gene conversion or some other unknown mechanism. A G-to-A RNA editing was observed in one lesional tissue without AEI. In addition, we observed correlations between the mutations in the four mevalonate pathway genes and clinical manifestations in the PK patients, which might support a new and simplified classification of PK under the guidance of genetic testing.DOI: http://dx.doi.org/10.7554/eLife.06322.001
Background Elderly atopic dermatitis (AD) is a newly defined subtype of AD stratified by age-related clinical pictures. Objectives To analyse the clinical features and molecular profile of elderly AD patients in China, comparing with infantile, childhood and adolescent/adult AD. Methods A total of 1312 patients diagnosed by Hanifin and Rajka diagnostic criteria of AD from Huashan Hospital, Shanghai, China, were divided into four groups by age (2-18, 19-40, 41-60 and >60 years), and clinical features were evaluated by questionnaire and physical examination. Serum total IgE, eosinophil counts and various cytokines were further analysed in some of the patients and healthy controls. Results Elderly AD showed significantly higher male/female ratio and rural/urban ratio than other age groups, and more than half of elderly AD first appeared after 60 years old. Skin lesions of elderly AD were more often seen in the trunk and extensor sites of the extremities. Level of serum IgE and eosinophil counts were significantly lower in elderly AD than those in other age groups. Serum levels of IL-4, TARC, IL-17A, IL-6, IL-22, IL-33 and TSLP were significantly higher in elderly AD patients than those of healthy controls, indicating a mixed Th2/Th17/Th22 inflammation. Conclusions Elderly AD demonstrated unique clinical characteristics compared with other age groups and showed mixed Th2/Th17/Th22 skewing, indicating a unique pathogenesis for elderly AD.
Allergen-specific immunotherapy is widely used for allergic rhinitis and asthma treatment worldwide. This study explored the efficacy and safety of sublingual immunotherapy (SLIT) with the extracts of Dermatophagoides Farinae (D. farinae Drops) on house dust mites (HDM)-induced atopic dermatitis (AD). 239 patients with HDM-induced AD were recruited and exposure to a multi-centre, randomized, double-blind, and placebo-controlled clinical trials for 36 weeks, which were randomly divided into placebo and sublingual D. farinae Drops groups (high-dose, medium-dose and low-dose), respectively. Statistical analysis was performed in three groups: Full Analysis Set, Per Protocol Set and Safety Set. 48 cases have withdrawn from the study before the end of study. As primary outcomes, significant decreases in scoring atopic dermatitis and total medication score were showed in medium-dose and high-dose D. farinae Drops groups. In the sixth visit, the skin lesion area showed a statistically significant difference between high-dose/medium-dose D. farinae Drops group and placebo group (p < .05). Most adverse events are slight, and no life-threatening adverse drug reaction happened. Our research demonstrates the beneficial effect of SLIT with high or medium dose D. farinae Drops on AD, and the treatment was well tolerated.
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