Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Adrenoleucodistrofia/genética , Mutação , Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP , Adolescente , Idade de Início , Sequência de Aminoácidos , Estudos de Casos e Controles , Sequência Conservada , Análise Mutacional de DNA , Pai , Heterozigoto , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Dados de Sequência Molecular , Mães , Mutação de Sentido Incorreto , Linhagem , Mutação Puntual , Estrutura Terciária de Proteína/genética , Homologia de Sequência de AminoácidosRESUMO
A large number of ABCD1 gene mutations have been reported all over the world, but not previously in India. We report on the first known patient with childhood cerebral adrenoleukodystrophy and a de novo 3' splice-site mutation in this gene. Magnetic resonance imaging of the brain revealed large, confluent, hyperintense areas in the bilateral cerebral white matter, predominantly parieto-occipital, with extensions into posterior regions that led to breakdown of the blood-brain barrier. An increased level of very long chain fatty acids was also consistent with the biochemical defect for adrenoleukodystrophy. Sequencing of the ABCD1 gene of this patient identified a 3' splice-site mutation in the intervening sequence 4 (-2a > g). We did not find any mutation in the gene of the proband's mother, which confirms its de novo occurrence.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Adrenoleucodistrofia/genética , Mutação , Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP , Adrenoleucodistrofia/patologia , Criança , Análise Mutacional de DNA , Humanos , Índia , Masculino , Reação em Cadeia da PolimeraseRESUMO
Nutritional deprivation of proteins decreases the protein kinase C (PKC) activity in rat lung. The activity of (PKC) is influenced by lipid metabolism. Changes in PKC activity may influence phosphorylation of its substrate proteins in the tissues. Therefore, alterations in phospholipid metabolism and PKC mediated protein phosphorylation in dietary protein deficiency in rat lung were envisaged. The study was conducted on rats fed on three different types of diet viz., casein (20% protein), deficient (4% protein, rice flour as source of protein) and supplemented (deficient diet supplemented with L-lysine and DL-threoning). Feeding of protein deficient diet caused reduction in incorporation of [3H] myo-inositol in the total phosphoinositides in lungs and an increase in total inositol phosphate pool. There was a significant reduction in the contents and turnover rate of phosphatidyl inositol and phosphatidyl inositol monophosphate. Supplementation of diet with L-lysine and DL-threonine had a reversing effect on total pool of phosphoinositides and, the metabolism of phosphatidyl inositol bisphosphate and phosphatidyl inositol. In phosphatidyl choline metabolism, the dietary protein deficiency led to a decrease in incorporation of [14C-methyl] choline-chloride in total phospholipids. In contrast, its incorporation increased in phosphatidyl choline pool. The contents of phosphatidyl choline and residue, incorporation of [14C-methyl] choline-chloride in them and their turnover rate also increased. Supplementation of diet had a reversal effect on most of these parameters. Phosphorylation of proteins of 84, 47, 35 and 16 kDa was identified to be mediated by PKC. In dietary protein deficiency, phosphorylation of all these proteins, except that of 47 kDa, increased. Supplementation of diet reversed the pattern except that of 84 kDa. The findings suggest that changes in phospholipid metabolism in dietary protein deficiency may effect the activity of PKC thereby influencing the phosphorylation of its substrate proteins and hence associated functions that may lead to pathophysiology of lung.
