Divergent metabolic phenotype between two sisters with congenital generalized lipodystrophy due to double AGPAT2 homozygous mutations. A clinical, genetic and in silico study

Simple item page
dc.contributor.authorCortés, V.A.
dc.contributor.authorSmalley, S.V.
dc.contributor.authorGoldenberg, D.
dc.contributor.authorLagos, C.F.
dc.contributor.authorHodgson, M.I.
dc.contributor.authorSantos, J.L.
dc.date.accessioned2023-05-19T20:46:31Z
dc.date.available2023-05-19T20:46:31Z
dc.date.issued2014
dc.description.abstractCongenital 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.fechaingreso.objetodigital2025-01-09
dc.fuente.origenORCID-mayo23
dc.identifier.doi10.1371/journal.pone.0087173
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/69800
dc.identifier.wosidWOS:000330621900074
dc.issue.numeroNo. 1
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final6
dc.pagina.inicio1
dc.revistaPLOS ONE
dc.rightsacceso abierto
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDivergent metabolic phenotype between two sisters with congenital generalized lipodystrophy due to double AGPAT2 homozygous mutations. A clinical, genetic and in silico studyes_ES
dc.typeartículo
dc.volumenVol. 9
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Divergent metabolic phenotype between two sisters with congenital generalized lipodystrophy due to double AGPAT2 homozygous mutations. A clinical, genetic and in silico study.pdf
Size:
511.75 KB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Artículos de revistas