Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease

Purpose: Lafora disease (LD) is an autosomal recessive form of progressive myoclonus epilepsy with onset in childhood or adolescence and with fatal outcome caused by mutations in two genes: EPM2A and NHLRC1. The aim of this study was to characterize the mutation spectrum in a cohort of unrelated patients with presumed LD. Methods: Sequencing of the two genes and search for large rearrangements was performed in 46 unrelated patients with suspected LD, 33 originating from France and the others from different countries. Patients were classified into two groups according to the clinical presentation. Results: Mutations of various types were found in EPM2A in 10 patients and in NHLRC1 in 4 patients. Mutations were found in 14 (93%) of 15 patients with classical clinical and electroencephalography (EEG) presentation of LD and in no patients with an atypical presentation. Ten mutations were novel, including the first substitution reported in a donor splice site of EPM2A, leading to the deletion of exon 2 at the RNA level. Four large deletions, including two deletions of exon 2 with different sizes and breakpoints, were found in EPM2A, corresponding to 20% of the alleles of this gene. Discussion: We described several novel mutations of EPM2A and NHLRC1 and brought additional data to the genetic epidemiology of LD. This study emphasized the high mutation rate in patients with classical LD as well as the high negativity rate of skin biopsy.     

Plakophilin-3-deficient mice develop hair coat abnormalities and are prone to cutaneous inflammation

We generated mice deficient in plakophilin-3 (PKP3), a member of the Armadillo-repeat family and a component of desmosomes and stress granules in epithelial cells. In these mice, several subsets of hair follicles (HFs) had morphological abnormalities, and the majority of awl and auchene hair shafts had fewer medullar air columns. Desmosomes were absent from the basal layer of the outer root sheath of HFs and from the matrix cells that are in contact with dermal papillae. In the basal layer of PKP3-null epidermis, densities of desmosomes and adherens junctions were remarkably altered. Compensatory changes in several junctional proteins were observed. PKP3-null mice housed in conventional facilities were prone to dermatitis. Our animal model provides in vivo evidence that PKP3 plays a critical role in morphogenesis of HFs and shafts and in limiting inflammatory responses in the skin.     

Bladder Mucosal Graft Vaginoplasty: A Case Report

Background

Female vaginoplasty reconstruction, by choice, is usually performed with adjacent tissue. However in some clinical conditions such as high urogenital confluence sinus, cloacal malformation with extreme vaginal hypoplasia, local tissue may not be available. When vaginal replacement is performed in pediatric patients intestinal segments is preferred to non-operative procedures that require continuative dilations. However mucus production, malignant transformation risk and diversion colitis are important side effects.

Bedside adherence to clinical practice guidelines for enteral nutrition in critically ill patients receiving mechanical ventilation: a prospective,multi-centre,observational study

Introduction  

The primary aim was to measure the amount of nutrients required, prescribed and actually administered in critically ill patients. Secondary aims were to assess adherence to clinical practice guidelines, and investigate factors leading to non-adherence.