Divergent metabolic phenotype between two sisters with congenital generalized lipodystrophy due to double AGPAT2 homozygous mutations. A clinical, genetic and in silico study
| dc.contributor.author | Cortés, V.A. | |
| dc.contributor.author | Smalley, S.V. | |
| dc.contributor.author | Goldenberg, D. | |
| dc.contributor.author | Lagos, C.F. | |
| dc.contributor.author | Hodgson, M.I. | |
| dc.contributor.author | Santos, J.L. | |
| dc.date.accessioned | 2023-05-19T20:46:31Z | |
| dc.date.available | 2023-05-19T20:46:31Z | |
| dc.date.issued | 2014 | |
| dc.description.abstract | 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. | |
| dc.fuente.origen | ORCID-mayo23 | |
| dc.identifier.doi | 10.1371/journal.pone.0087173 | |
| dc.identifier.uri | https://repositorio.uc.cl/handle/11534/69800 | |
| dc.language.iso | en | |
| dc.title | Divergent metabolic phenotype between two sisters with congenital generalized lipodystrophy due to double AGPAT2 homozygous mutations. A clinical, genetic and in silico study | es_ES |
| dc.type | artículo |