Identification of an interstitial 18p11.32-p11.31 duplication including the EMILIN2 gene in a family with porokeratosis of Mibelli.

Porokeratosis is a rare disease of epidermal keratinization characterized by the histopathological feature of the cornoid lamella, a column of tightly fitted parakeratocytic cells, whose etiology is still unclear. Porokeratosis of Mibelli is a subtype of porokeratosis presenting a single plaque or a small number of plaques of variable size located unilaterally on limbs. It frequently appears in childhood and occurs with a higher incidence in males. Cytogenetic analyses were performed in all members of the family on lesioned and uninvolved skin. An array-CGH analysis was also performed utilizing the Human Genome CGH Microarray Kit G3 400 with 5.3 KB overall median probe spacing. Gene expression was performed on skin fibroblasts. In this study, we describe a Caucasian healthy 4-year-old child and his father showing features of porokeratosis of Mibelli. Array-CGH analysis revealed an interstitial 429.5 Kb duplication of chromosome 18p11.32-p11.3 containing four genes, namely: SMCHD1, EMILIN2, LPIN2, and MYOM1 both in patient and his father. EMILIN2 resulted overexpressed on skin fibroblasts. Also other members of this family, without evident signs of porokeratosis, carried the same duplication. Among these genes, we focused our attention on elastin microfibril interfacer 2 (EMILIN2) gene. Apoptosis plays a fundamental role in maintaining epidermal homeostasis, balancing keratinocytes proliferation, and forming the stratum corneum. EMILIN2 is known to trigger the apoptosis of different cell lines negatively affecting cell survival. It is expressed in the skin. We could speculate that the duplication and overexpression of EMILIN2 cause an abnormal apoptosis of epidermal keratinocytes and alter the process of keratinization, even if other epigenetic and genetic factors could also be involved. Our results could contribute to a better understanding of the pathogenesis of porokeratosis of Mibelli

Asymmetric cavernous sinus enlargement: a novel finding in Sturge-Weber syndrome

Enlargement of deep cerebral veins and choroid plexus engorgement are frequently reported in Sturge-Weber syndrome. We aim to describe cavernous sinus involvement in patients with this syndrome and to identify possible clinical-neuroimaging correlations

Clinical images.

<p>A) Clinical image revealing a whitish-red plaque on the lower right leg of the 4-year-old proband. The affected area is made up of numerous whitish-red round papules that coalesce into irregular plaque and single papules, the area perimeter defined by a whitish border and cleaved by a central furrow. Slightly raised whitish-red portions can also be observed. B) Enlarged detail of the lesion. C) The patient's skin biopsy shows slight papillomatosis and ortokeratosis of epidermis and a cornoid lamella; the derma appears normal (H&E, 10×). D) A column of parakeratotic cells makes up the cornoid lamella (H&E, 200×). E) The examination of the skin biopsy of the father shows atrophic epidermis with two cornoid lamellae; solar elastosis and sparse perivascular lymphocytic infiltrate can be recognized (H&E, 10×). F) The cornoid lamella is very thin (H&E, 200×).</p

Array-CGH results.

<p>A) Result of array-CGH analysis of chromosome 18 with Agilent Human Genome CGH microarray Kit G3 400K. The 18p11.32p11.31 duplicated region extends between oligomers A_16_P20755613 (2,724,439 bp) and A_16_P40933037 (3,153,981 bp) B) Gene contents of the duplicated region.</p

Expression studies.

<p>Comparison <i>of EMILIN2, LPIN2</i>, and <i>MAD1L1</i> expression in the primary skin fibroblast cultures of proband's father compared with controls (Ct). The histogram shows the median of values: dark grey corresponds to patient's fibroblasts (#102) normalized to the median of values of six normal control's fibroblasts (light grey).</p

Additional file 1: of Topical corticosteroid phobia in parents of pediatric patients with atopic dermatitis: a multicentre survey

Univariate and multivariate analysis results (dependent variable: TCS fear). (DOCX 22 kb