Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations.

BACKGROUND: Genetic mutations in the plectin gene (PLEC) cause autosomal recessive forms of epidermolysis bullosa simplex (EBS) associated with either muscular dystrophy (EBS-MD) or pyloric atresia (EBS-PA). Phenotype-genotype analysis has suggested that EBS-MD is due mostly to genetic mutations affecting the central rod domain of plectin, and EBS-PA to mutations outside this domain. OBJECTIVES: This study aimed to describe new phenotypes of patients with EBS-MD and EBS-PA, to identify novel PLEC mutations and to establish genotype-phenotype correlations. METHODS: Seven patients with a suspicion of EBS linked to PLEC mutations were included. A standardized clinical questionnaire was sent to the physicians in charge of each patient. Immunofluorescence studies of skin biopsies followed by molecular analysis of PLEC were performed in all patients. RESULTS: We report the first case of nonlethal EBS-PA improving with age, the first multisystemic involvement in a patient with lethal EBS-PA, and the first patients with EBS-MD with involvement of either the bladder or oesophagus. Eleven novel PLEC mutations are also reported. CONCLUSIONS: Our results confirm that EBS-PA is linked to mutations in the distal exons 1-30 and 32 of PLEC. Long-term survival is possible, with skin improvement, but a delayed onset of MD is probable. While EBS-MD is linked to PLEC mutations in all exons, in most cases one of the mutations affects exon 31. The precocity of MD seems to be linked to the type and localization of the PLEC mutation(s), but no correlation with mucosal involvement has been found.

Plasmapheresis treatment for recurrent focal sclerosis in pediatric renal allografts.

Recurrence of focal segmental glomerulosclerosis (FSGS) in pediatric renal allografts is associated with a poor graft survival. This study reports on plasmapheresis for the treatment of recurrent FSGS in pediatric renal transplant recipients. The records of 100 consecutive pediatric (age <21 years) renal transplants were reviewed. Twenty patients had FSGS as the cause of renal failure. Eight of these (40%) had a recurrence (proteinuria >1 g/m2 per day) within 1 month of transplantation. Five of six patients treated with plasmapheresis went into remission (<0.2 g/m2 per day), receiving a total of 42+/-26 (12-73) sessions, with the mean number of sessions required to achieve a remission being 24+/-17 (8-51). One patient had a second recurrence 1 year following cessation of plasmapheresis and responded to another course of plasmapheresis. The 1 patient who did not respond to plasmapheresis had a delay in initiation of therapy of 42 days. Plasmapheresis initiated within 48 h of recurrence resulted in earlier remissions and improved graft survival among our patients. Plasmapheresis appears to be effective in treating recurrent FSGS following kidney transplantation and should be started as soon as possible. The number of plasmapheresis sessions used to achieve remission should be adjusted according to response rather than adhering to a fixed protocol.

Expression of a 65 kda oncofetal phosphoprotein in the altered hepatic foci of rats fed 2-acetylaminofluorene followed by phenobarbital.

The altered hepatic foci (AHF) developed in livers of Sprague-Dawley male rats,by acetylaminofluorene/phenobarbital protocol, were analyzed on paraffin sections for gamma-glutamyl-transpeptidase, glutathione S-transferase P and 65 kDa oncofetal protein (p65). 92% percent of the foci were GST-P-positive, 89% of those were also positive for GGT but only 10-12% were positive for p65. Comparison of tissues from different sources such as fetal and normal liver, foci, nodules, surrounding parenchyma and hepatocellular carcinomas revealed the presence of p65 protein in all tissues except normal rat liver and liver parenchyma surrounding the focal lesions.