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Background: Atopic dermatitis (AD) is characterized by flares of eczematous lesions accompanied by intense pruritus, which can tremendously impact quality of life (QoL). Despite continuous therapeutic progress, there are still unmet needs regarding AD management., Objective: This sub-analysis of the cross-sectional global study MEASURE-AD with 1558 AD patients treated with or eligible for systemic therapy aimed at characterizing the real-world burden of 98 patients in Austria and Switzerland. Patients were enrolled between October 2019 and June 2020. Assessing patient characteristics, treatment, disease severity, and patient-reported outcomes., Results: Mean age at time of diagnosis was 19.4 years with delayed diagnosis by an average of almost 3 years. All patients obtained treatment, 57.1% of them systemic therapy, mostly dupilumab. 45.9%-73.5% of all patients presented with moderate to severe disease and more than half of them suffered from moderate to severe pruritus, impaired QoL, and had experienced several flares. Furthermore, a negative impact on sleep, mental health, social life, and work productivity was revealed., Conclusions: This analysis confirms that AD is associated with a multidimensional burden despite treatment and demonstrates unmet needs regarding diagnostic delay, under-treatment with systemic therapy, and the development of efficacious therapies to improve clinical symptoms and QoL.

OFD1, now recognized as a ciliopathy, is characterized by malformations of the face, oral cavity and digits, and is transmitted as an X-linked condition with lethality in males. Mutations in OFD1 also cause X-linked Joubert syndrome (JBTS10) and Simpson-Golabi-Behmel syndrome type 2 (SGBS2). We have studied 55 sporadic and six familial cases of suspected OFD1. Comprehensive mutation analysis in OFD1 revealed mutations in 37 female patients from 30 families; 22 mutations have not been previously described including two heterozygous deletions spanning OFD1 and neighbouring genes. Analysis of clinical findings in patients with mutations revealed that oral features are the most reliable diagnostic criteria. A first, detailed evaluation of brain MRIs from seven patients with cognitive defects illustrated extensive variability with the complete brain phenotype consisting of complete agenesis of the corpus callosum, large single or multiple interhemispheric cysts, striking cortical infolding of gyri, ventriculomegaly, mild molar tooth malformation and moderate to severe cerebellar vermis hypoplasia. Although the OFD1 gene apparently escapes X-inactivation, skewed inactivation was observed in seven of 14 patients. The direction of skewing did not correlate with disease severity, reinforcing the hypothesis that additional factors contribute to the extensive intrafamilial variability., (© 2012 Wiley Periodicals, Inc.)

ATOH8 is a bHLH domain transcription factor implicated in the development of the nervous system, kidney, pancreas, retina and muscle. In the present study, we collected sequence of ATOH8 orthologues from 18 vertebrate species and 24 invertebrate species. The reconstruction of ATOH8 phylogeny and sequence analysis showed that this gene underwent notable divergences during evolution. For those vertebrate species investigated, we analyzed the gene structure and regulatory elements of ATOH8. We found that the bHLH domain of vertebrate ATOH8 was highly conserved. Mammals retained some specific amino acids in contrast to the non-mammalian orthologues. Mammals also developed another potential isoform, verified by a human expressed sequence tag (EST). Comparative genomic analyses of the regulatory elements revealed a replacement of the ancestral TATA box by CpG-islands in the eutherian mammals and an evolutionary tendency for TATA box reduction in vertebrates in general. We furthermore identified the region of the effective promoter of human ATOH8 which could drive the expression of EGFP reporter in the chicken embryo. In the opossum, both the coding region and regulatory elements of ATOH8 have some special features, such as the unique extended C-terminus encoded by the third exon and absence of both CpG islands and TATA elements in the regulatory region. Our gene mapping data showed that in human, ATOH8 was hosted in one chromosome which is a fusion product of two orthologous chromosomes in non-human primates. This unique chromosomal environment of human ATOH8 probably subjects its expression to the regulation at chromosomal level. We deduce that the great interspecific differences found in both ATOH8 gene sequence and its regulatory elements might be significant for the fine regulation of its spatiotemporal expression and roles of ATOH8, thus orchestrating its function in different tissues and organisms.