A case of focal facial dermal dysplasia type 4.

We present a rare case of focal facial dermal dysplasia type 4 (FFDD4) in an otherwise healthy boy infant, presenting as bilateral preauricular scarlike defects surrounded by a hair collar, resembling membranous aplasia cutis congenita. The presence of a hair collar supports the hypothesis that FFDD is caused by abnormal closure at facial embryonic fusion lines, but unlike midline scalp defects is not associated with neurological compromise. Other types of FFDD occur at different sites and can be associated with cranial dysgraphism. Awareness of this rare condition by dermatologists is imperative to enable prompt recognition and minimize diagnostic delay.

Sweet's syndrome with pulmonary involvement.

Sweet's syndrome is an acute febrile neutrophilic dermatosis with classical clinical features. Systemic manifestations in Sweet's syndrome including fever, arthralgia, myalgia and ocular involvement are common. Pulmonary involvement is a rare manifestation that has been reported previously in 34 cases and can be fatal if left untreated. We report a striking case of Sweet's syndrome with respiratory failure secondary to bilateral pulmonary interstitial infiltrates, which rapidly responded to intravenous corticosteroid therapy. This case is an important reminder of the systemic manifestations of Sweet's syndrome and highlights the value of collaboration between different medical specialities to optimise patient management and outcomes.

Case of keratoacanthoma centrifugum marginatum treated with acitretin.

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma (KA), characterised by a progressively expanding tumour with a lack of spontaneous remission and significant scarring. KCM has been reported previously in less than 50 cases worldwide. We present the case of a large solitary KCM on the right shin of a 71-year-old woman. This was treated successfully with oral acitretin for 16 months with sustained remission at 24 months. Our case provides further supporting evidence for acitretin as a useful treatment for KCM to induce remission, prevent extensive surgery and minimise destructive scarring.

A Case of Hereditary Leiomyomatosis and Renal Cell Carcinoma.

A 49-year-old lady presented with multiple recurring painful lesions over her thighs, arms, and back. Past medical history included a left sided nephrectomy for renal cell carcinoma and a hysterectomy for multiple uterine fibroids (leiomyomas). Histopathological examination revealed changes consistent with pilar leiomyomas. Gene mutation analysis confirmed a diagnosis of hereditary leiomyomatosis and renal cell carcinoma. Hereditary leiomyomatosis and renal cell carcinoma is an uncommon autosomal dominant condition characterised by the concurrent presentation of cutaneous and uterine leiomyomas. Renal cell carcinoma associated with this condition is more aggressive and a significant cause of mortality. Due to this association with potentially fatal renal cell carcinoma we felt that it was important to highlight this case with an update on pathophysiology and management.

Mapping of internal ribosome entry sites (IRES).

The dicistronic luciferase reporter gene system is the most common method to isolate and characterize internal ribosome entry sites (IRES). It is based on the expression of a dicistronic RNA comprising two independent reporter genes in 3' and 5'cistrons, and the putative IRES inserted into intercistronic region. The most convenient aspect of using Renilla and firefly luciferase genes is that both gene products can be detected in a single assay using Dual-Luciferase(®) Reporter Assay System from Promega. The Renilla luciferase coding sequence is often inserted into the 5'cistron and serves as internal control. It is translated cap dependently, as it is close to the cap structure at the 5' end. The 3'cistron located far downstream to the cap structure can only be translated by a cap-independent mechanism when the intercistronic sequence is capable of ribosome binding and re-initiation of translation. Expression level of the 3'cistron is usually normalized to the expression of 5'cistron to estimate the relative IRES activity of intercistronic sequences.

JKTBP1 is involved in stabilization and IRES-dependent translation of NRF mRNAs by binding to 5' and 3' untranslated regions.

Heterogeneous nuclear ribonucleoprotein D-like protein (JKTBP) 1 was implicated in cap-independent translation by binding to the internal ribosome entry site in the 5' untranslated region (UTR) of NF-κB-repressing factor (NRF). Two different NRF mRNAs have been identified so far, both sharing the common 5' internal ribosome entry site but having different length of 3' UTRs. Here, we used a series of DNA and RNA luciferase reporter constructs comprising 5', 3' or both NRF UTRs to study the effect of JKTBP1 on translation of NRF mRNA variants. The results indicate that JKTBP1 regulates the level of NRF protein expression by binding to both NRF 5' and 3' UTRs. Using successive deletion and point mutations as well as RNA binding studies, we define two distinct JKTBP1 binding elements in NRF 5' and 3' UTRs. Furthermore, JKTBP1 requires two distinct RNA binding domains to interact with NRF UTRs and a short C-terminal region for its effect on NRF expression. Together, our study shows that JKTBP1 contributes to NRF protein expression via two disparate mechanisms: mRNA stabilization and cap-independent translation. By binding to 5' UTR, JKTBP1 increases the internal translation initiation in both NRF mRNA variants, whereas its binding to 3' UTR elevated primarily the stability of the major NRF mRNA. Thus, JKTBP1 is a key regulatory factor linking two pivotal control mechanisms of NRF gene expression: the cap-independent translation initiation and mRNA stabilization.