Browsing by Author "Lagos, C.F."
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- ItemDivergent metabolic phenotype between two sisters with congenital generalized lipodystrophy due to double AGPAT2 homozygous mutations. A clinical, genetic and in silico study(2014) Cortés, V.A.; Smalley, S.V.; Goldenberg, D.; Lagos, C.F.; Hodgson, M.I.; Santos, J.L.Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by extreme reduction of white adipose tissue (WAT) mass. CGL type 1 is the most frequent form and is caused by mutations in AGPAT2. Genetic and clinical studies were performed in two affected sisters of a Chilean family. These patients have notoriously dissimilar metabolic abnormalities that correlate with differential levels of circulating leptin and soluble leptin receptor fraction. Sequencing of AGPAT2 exons and exon-intron boundaries revealed two homozygous mutations in both sisters. Missense mutation c.299G>A changes a conserved serine in the acyltransferase NHX4D motif of AGPAT2 (p.Ser100Asn). Intronic c.493-1G>C mutation destroy a conserved splicing site that likely leads to exon 4 skipping and deletion of whole AGPAT2 substrate binding domain. In silico protein modeling provided insights of the mechanisms of lack of catalytic activity owing to both mutations.
- ItemMolecular modeling of Trypanosoma cruzi glutamate cysteine ligase and investigation of its interactions with glutathione(2012) Lagos, C.F.; Araya-Secchi, R.; Thomas, P.; Pérez-Acle, T.; Tapia, R.A.; Salas Sanchez, Cristian Osvaldo