Risk of attention-deficit/hyperactivity disorder in children with atopic dermatitis

Atopic dermatitis (AD) is a common, chronic, inflammatory, pruritic skin disorder that affects up to 20% of the children in Western countries. Attention-Deficit/Hyperactivity disorder (ADHD) has been reported to be more frequent in children with AD. The purpose of this study was to explore the risk for ADHD in our population of patients with AD. A population-based case-control study, using the medical database of Clalit Health Services (CHS), the largest healthcare provider organization in Israel. The study included 840 patients with AD between the age of 0-18 years and 900 age and gender frequency-matched patients without AD. The proportion of ADHD in patients with AD was 7.1% as compared to 4.1% in controls. ADHD was more frequent in boys with AD (9.6% vs. 5.2%, odds ratio (OR) 1.9, 95% confidence interval (CI) 1.1-3.2) but not in girls with AD (4.6% vs. 2.9% OR 1.5). In multivariate analyses, AD was associated with ADHD (OR 2.1, 95% CI 1.3-3.4). The current study demonstrated an association between AD and ADHD. This report and earlier observations emphasize the need for detection and treatment of ADHD in atopic patients.  </p

Autosomal Recessive Ichthyosis with Hypotrichosis Caused by a Mutation in ST14, Encoding Type II Transmembrane Serine Protease Matriptase

In this article, we describe a novel autosomal recessive ichthyosis with hypotrichosis syndrome, characterized by congenital ichthyosis associated with abnormal hair. Using homozygosity mapping, we mapped the disease locus to 11q24.3-q25. We screened the ST14 gene, which encodes matriptase, since transplantation of skin from matriptase(−/−)-knockout mice onto adult athymic nude mice has been shown elsewhere to result in an ichthyosislike phenotype associated with almost complete absence of erupted pelage hairs. Mutation analysis revealed a missense mutation, G827R, in the highly conserved peptidase S1–S6 domain. Marked skin hyperkeratosis due to impaired degradation of the stratum corneum corneodesmosomes was observed in the affected individuals, which suggests that matriptase plays a significant role in epidermal desquamation

Mutations in CSTA, Encoding Cystatin A, Underlie Exfoliative Ichthyosis and Reveal a Role for This Protease Inhibitor in Cell-Cell Adhesion

Autosomal-recessive exfoliative ichthyosis presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of nonerythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Using whole-genome homozygosity mapping, candidate-gene analysis and deep sequencing, we have identified loss-of-function mutations in the gene for protease inhibitor cystatin A (CSTA) as the underlying genetic cause of exfoliative ichthyosis. We found two homozygous mutations, a splice-site and a nonsense mutation, in two consanguineous families of Bedouin and Turkish origin. Electron microscopy of skin biopsies from affected individuals revealed that the level of detachment occurs in the basal and lower suprabasal layers. In addition, in vitro modeling suggests that in the absence of cystatin A protein, there is a cell-cell adhesion defect in human keratinocytes that is particularly prominent when cells are subject to mechanical stress. We show here evidence of a key role for a protease inhibitor in epidermal adhesion within the lower layers of the human epidermis

Mutations in CSTA, Encoding Cystatin A, Underlie Exfoliative Ichthyosis and Reveal a Role for This Protease Inhibitor in Cell-Cell Adhesion

Autosomal-recessive exfoliative ichthyosis presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of nonerythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Using whole-genome homozygosity mapping, candidate-gene analysis and deep sequencing, we have identified loss-of-function mutations in the gene for protease inhibitor cystatin A (CSTA) as the underlying genetic cause of exfoliative ichthyosis. We found two homozygous mutations, a splice-site and a nonsense mutation, in two consanguineous families of Bedouin and Turkish origin. Electron microscopy of skin biopsies from affected individuals revealed that the level of detachment occurs in the basal and lower suprabasal layers. In addition, in vitro modeling suggests that in the absence of cystatin A protein, there is a cell-cell adhesion defect in human keratinocytes that is particularly prominent when cells are subject to mechanical stress. We show here evidence of a key role for a protease inhibitor in epidermal adhesion within the lower layers of the human epidermis