Rombencefalosinapsis, una rara alteración del desarrollo del cerebelo de fácil diagnóstico / Rhombencephalosynapsis, a rare congenital abnormality easy to diagnose

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Effect of nicotine on ATPase, catalase and calcium levels in the presence of oligoelements in brain regions of young rats.

UNLABELLED: The effect of nicotine on membrane alterations and fluidity changes in very young models remains unclear. The aim of this study was to evaluate the effect of nicotine on total ATPase, H(2)O(2) and calcium in brain of young rats in the presence of oligoelements. Male Wistar rats (weight 80 g) received intraperitoneally either a single dose or repeated doses for 4 days as follows: Group 1 (control) NaCl 0.9%; group 2 nicotine (1mg/kg); group 3 oligoelements (50 µl); and group 4 nicotine (1mg/kg) + oligoelements (50 µl). The brain regions (cortex, hemispheres and cerebellum + medulla oblongata) of each rat were then obtained to measure the concentrations of total ATPase, H(2)O(2) and calcium using spectrophotometric methods. RESULTS: Total ATPase increased significantly (p < 0.05) in groups treated with oligoelements in repeated doses in hemisphere region, and in groups that received oligoelements + nicotine in single or repeated doses in medulla oblongata. Catalase showed significant decreased in cerebellum/medulla oblongata. Results suggest that nicotine induces changes in membrane fluidity in brain of young rats, and that ATPase could be a biomarker of nicotine consumption in young subjects.

LMNA mutation in progeroid syndrome in association with strokes.

Hutchinson-Gilford progeria syndrome is a very rare but well-characterized genetic disorder that causes premature ageing. Clinical features affect growth, skeleton, body fat, skin, hair and the cardiovascular system. It is caused by mutations in LMNA gene, the most frequent being p.Gly608Gly (c.1824C > T) in exon 11. Here we present a four-year-old HGPS patient who presented several severe strokes and carried a heterozygous LMNA missense mutation in exon 2: p.Glu138Lys. This mutation is located far from the C-terminal region implicated in the posttranslational processing of prelamin A, but it lies within the rod domain of lamin A/C that represents a highly conserved domain specific to nuclear lamins. We hypothesize that this region could be involved in early and severe strokes in HGPS, such as those presented by our patient.

Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.

The Sanfilippo syndrome type C [mucopolysaccharidosis IIIC (MPS IIIC)] is caused by mutations in the HGSNAT gene, encoding an enzyme involved in heparan sulphate degradation. We report the first molecular study on several Spanish Sanfilippo syndrome type C patients. Seven Spanish patients, one Argentinean and three Moroccan patients were analysed. All mutant alleles were identified and comprised nine distinct mutant alleles, seven of which were novel, including four missense mutations (p.A54V, p.L113P, p.G424V and p.L445P) and three splicing mutations due to two point mutations (c.633+1G>A and c.1378-1G>A) and an intronic deletion (c.821-31_821-13del). Furthermore, we found a new single nucleotide polymorphism (SNP) (c.564-98T>C). The two most frequent changes were the previously described c.372-2A>G and c.234+1G>A mutations. All five splicing mutations were experimentally confirmed by studies at the RNA level, and a minigene experiment was carried out in one case for which no fibroblasts were available. Expression assays allowed us to show the pathogenic effect of the four novel missense mutations and to confirm that the already known c.710C>A (p.P237Q) is a non-pathogenic SNP. Haplotype analyses suggested that the two mutations (c.234+1G>A and c.372-2A>G) that were present in more than one patient have a common origin, including one (c.234+1G>A) that was found in Spanish and Moroccan patients.