Exome sequencing in developmental eye disease leads to identification of causal variants in GJA8, CRYGC,PAX6 and CYP1B1

Developmental eye diseases, including cataract/microcornea, Peters anomaly and coloboma/microphthalmia/anophthalmia, are caused by mutations encoding many different signalling and structural proteins in the developing eye. All modes of Mendelian inheritance occur and many are sporadic cases, so provision of accurate recurrence risk information for families and affected individuals is highly challenging. Extreme genetic heterogeneity renders testing for all known disease genes clinically unavailable with traditional methods. We used whole-exome sequencing in 11 unrelated developmental eye disease patients, as it provides a strategy for assessment of multiple disease genes simultaneously. We identified five causative variants in four patients in four different disease genes, GJA8, CRYGC, PAX6 and CYP1B1. This detection rate (36%) is high for a group of patients where clinical testing is frequently not undertaken due to lack of availability and cost. The results affected clinical management in all cases. These variants were detected in the cataract/microcornea and Peters anomaly patients. In two patients with coloboma/microphthalmia, variants in ABCB6 and GDF3 were identified with incomplete penetrance, highlighting the complex inheritance pattern associated with this phenotype. In the coloboma/microphthalmia patients, four other variants were identified in CYP1B1, and CYP1B1 emerged as a candidate gene to be considered as a modifier in coloboma/microphthalmia.     

Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome

Prostate cancer is the second leading cause of cancer death among United States men. However, disease aggressiveness is varied, with low-grade disease often being indolent and high-grade cancer accounting for the greatest density of deaths. Outcomes are also disparate among men with high-grade prostate cancer, with upwards of 65% having disease recurrence even after primary treatment. Identification of men at risk for recurrence and elucidation of the molecular processes that drive their disease is paramount, as these men are the most likely to benefit from multimodal therapy. We previously showed that androgen-induced expression profiles in prostate development are reactivated in aggressive prostate cancers. Herein, we report the down-regulation of one such gene, Sparcl1, a secreted protein, acidic and rich in cysteine (SPARC) family matricellular protein, during invasive phases of prostate development and regeneration. We further demonstrate a parallel process in prostate cancer, with decreased expression of SPARCL1 in high-grade/metastatic prostate cancer. Mechanistically, we demonstrate that SPARCL1 loss increases the migratory and invasive properties of prostate cancer cells through Ras homolog gene family, member C (RHOC), a known mediator of metastatic progression. By using models incorporating clinicopathologic parameters to predict prostate cancer recurrence after treatment, we show that SPARCL1 loss is a significant, independent prognostic marker of disease progression. Thus, SPARCL1 is a potent regulator of cell migration/invasion and its loss is independently associated with prostate cancer recurrence.     

Recommendations for the practice of travel medicine

Travel Medicine has emerged as a distinct entity over the last two decades in response to a very substantial increase in international travel and is now forging its own identity, remit and objectives for care of the traveller. Crucial to the formation of any speciality is the definition of recommendations for its practice. This is particularly important and needed for travel medicine as it overlaps with and forms part of day-to-day work in a number of different medical specialities. This document defines a set of recommendations for the practice of travel medicine from the Faculty of Travel Medicine of the Royal College of Physicians and Surgeons of Glasgow. Their objective is to help raise standards of practice and achieve greater uniformity in provision of services, better to protect those who travel. As travel medicine moves towards applying for speciality status, these standards will also contribute to that process.     

A guide to choosing a burn scar rating scale for clinical or research use

Introduction

A lack of high quality burn scar rating scales underpins the urgent need to introduce a guide for clinicians and researchers to choose the most appropriate scale for their requirements.

Methods

An updated electronic search of Medline, CINAHL, and EMBASE databases from 2010 to 2011 of a previous published systematic review were used to identify English articles related to burn scar rating scales. The clinimetric properties, content, purpose, characteristics of the subjects tested and feasibility of each scale were critically reviewed.

Results

An additional seven papers were identified by the updated search, bringing the total number of papers reviewed to 36. The majority (88%) covered items pertaining to the physical properties of the skin rated by an observer. All of the scales had been tested for the purpose of discriminating between patient groups; however, only preliminary evidence exists for the ability of the scales to measure change in scar properties over time. The majority of testing of scales occurred using Caucasian subjects, males, upper limb sites and adults.

Conclusions

This paper provides a guide to selecting the most appropriate burn scar rating scale for research and clinical practice by reviewing the content, purpose, test sample characteristics and feasibility of each scale.