Mutational spectrum of Duchenne muscular dystrophy in Spain: Study of 284 cases. / Espectro mutacional de la distrofia muscular de Duchenne en España: estudio de 284 casos.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disease that affects one in 3500 live-born males. The total absence of dystrophin observed in DMD patients is generally caused by mutations that disrupt the reading frame of the DMD gene, and about 80% of cases harbour deletions or duplications of one or more exons. METHODS: We reviewed 284 cases of males with a genetic diagnosis of DMD between 2007 and 2014. These patients were selected from 8 Spanish reference hospitals representing most areas of Spain. Multiplex PCR, MLPA, and sequencing were performed to identify mutations. RESULTS: Most of these DMD patients present large deletions (46.1%) or large duplications (19.7%) in the dystrophin gene. The remaining 34.2% correspond to point mutations, and half of these correspond to nonsense mutations. In this study we identified 23 new mutations in DMD: 7 large deletions and 16 point mutations. CONCLUSIONS: The algorithm for genetic diagnosis applied by the participating centres is the most appropriate for genotyping patients with DMD. The genetic specificity of different therapies currently being developed emphasises the importance of identifying the mutation appearing in each patient; 38.7% of the cases in this series are eligible to participate in current clinical trials.

Effects of anisomycin on inhibitory avoidance in male and female CD1 mice.

The antibiotic anisomycin inhibits protein synthesis, which much research has suggested is required for the formation of long-term memory. The present work studied the effects of acute subcutaneous administration of anisomycin on the consolidation of memory in an inhibitory avoidance task in CD1 mice of both sexes. The animals were separated by sex and randomly distributed into three groups: two groups were injected with 150 mg/kg anisomycin, one immediately after the training phase and the other 24 h later, while the control group received saline. The interval between training and test was four days. Anisomycin administrated immediately after training produced statistically significant impairment of memory, which was not observed when the drug was administered 24 h after training. No sex differences were observed in the effects of anisomycin. These results extend to female mice the memory impairing effects of anisomycin previously observed in males and endorse the hypothesis that the establishment of long-term memory depends on protein synthesis shortly after training.

Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitus.

BACKGROUND AND METHODS: In the search for new factors of cardiovascular risk associated to diabetes mellitus (DM), special attention has been paid in recent years to hyperhomocysteinaemia. Therefore, we have established the concentration of homocysteine (Hcy) and other biochemical parameters in the plasma of a group of 57 type 1 and 32 type 2 diabetic patients and 54 control subjects and studied whether plasmatic homocysteinaemia was related to macroangiopathy, nephropathy, retinopathy and neuropathy. Because of significant differences for plasma Hcy values between men and women in the control group, we distinguished between both groups throughout the study. RESULTS: Patients with DM had higher Hcy than control subjects (11.7+/-5.4 vs. 10.1+/-2.4 micromol/l, p<0.05). Fasting hyperhomocysteinaemia was considered as the mean of the plasma Hcy for control subjects+2 SD (14.9 micromol/l in total group, 15.6 micromol/l in males and 13.9 micromol/l in females). In the studied groups with complications, we found significant differences between normohomocysteinaemic type 1 diabetic patients and those considered hyperhomocysteinaemic by us. On the other hand, patients having type 1 DM and complications had higher plasmatic Hcy concentration than those with no complications. CONCLUSIONS: We have found a relationship between high Hcy levels and prevalence of macroangiopathy, retinopathy and nephropathy in the type 1 diabetic patients, which was not been observed in the type 2 diabetic patients of our study. As a result, we consider plasmatic Hcy a complication-risk indicator in type 1 DM, and we recommend its use together with already established biochemical parameters in the control of the evolution of the disease.