We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Divergent Metabolic Phenotype between Two Sisters with Congenital Generalized Lipodystrophy Due to Double AGPAT2 Homozygous Mutations. A Clinical, Genetic and <i>In Silico</i> Study.
- Authors
Cortés, Víctor A.; Smalley, Susan V.; Goldenberg, Denisse; Lagos, Carlos F.; Hodgson, María I.; Santos, José L.
- 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.
- Subjects
LIPODYSTROPHY; METABOLISM; GENETIC mutation; GENETIC disorders; SISTERS; CHILEANS; LEPTIN receptors; DISEASES
- Publication
PLoS ONE, 2014, Vol 9, Issue 1, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0087173