Molecular analysis and intestinal expression of SAR1 genes and proteins in Anderson's disease (Chylomicron retention disease). - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Orphanet Journal of Rare Diseases Année : 2011

Molecular analysis and intestinal expression of SAR1 genes and proteins in Anderson's disease (Chylomicron retention disease).

Thomas Aparicio
  • Fonction : Auteur
  • PersonId : 918754
Eric Bruckert
  • Fonction : Auteur
  • PersonId : 906880

Résumé

BACKGROUND: Anderson's disease (AD) or chylomicron retention disease (CMRD) is a very rare hereditary lipid malabsorption syndrome. In order to discover novel mutations in the SAR1B gene and to evaluate the expression, as compared to healthy subjects, of the Sar1 gene and protein paralogues in the intestine, we investigated three previously undescribed individuals with the disease. METHODS: The SAR1B, SAR1A and PCSK9 genes were sequenced. The expression of the SAR1B and SAR1A genes in intestinal biopsies of both normal individuals and patients was measured by RTqPCR. Immunohistochemistry using antibodies to recombinant Sar1 protein was used to evaluate the expression and localization of the Sar1 paralogues in the duodenal biopsies. RESULTS: Two patients had a novel SAR1B mutation (p.Asp48ThrfsX17). The third patient, who had a previously described SAR1B mutation (p.Leu28ArgfsX7), also had a p.Leu21dup variant of the PCSK9 gene. The expression of the SAR1B gene in duodenal biopsies from an AD/CMRD patient was significantly decreased whereas the expression of the SAR1A gene was significantly increased, as compared to healthy individuals. The Sar1 proteins were present in decreased amounts in enterocytes in duodenal biopsies from the patients as compared to those from healthy subjects. CONCLUSIONS: Although the proteins encoded by the SAR1A and SAR1B genes are 90% identical, the increased expression of the SAR1A gene in AD/CMRD does not appear to compensate for the lack of the SAR1B protein. The PCSK9 variant, although reported to be associated with low levels of cholesterol, does not appear to exert any additional effect in this patient. The results provide further insight into the tissue-specific nature of AD/CMRD.

Domaines

Génétique
Fichier principal
Vignette du fichier
1750-1172-6-1.pdf (1.75 Mo) Télécharger le fichier
1750-1172-6-1-S1.DOC (113.5 Ko) Télécharger le fichier
1750-1172-6-1-S2.DOC (61 Ko) Télécharger le fichier
1750-1172-6-1.xml (126.99 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Format : Autre
Format : Autre
Format : Autre
Loading...

Dates et versions

inserm-00663694 , version 1 (27-01-2012)

Identifiants

Citer

Amandine Georges, Jessica Bonneau, Dominique Bonnefont-Rousselot, Jacqueline Champigneulle, Jean Rabès, et al.. Molecular analysis and intestinal expression of SAR1 genes and proteins in Anderson's disease (Chylomicron retention disease).. Orphanet Journal of Rare Diseases, 2011, 6 (1), pp.1. ⟨10.1186/1750-1172-6-1⟩. ⟨inserm-00663694⟩
235 Consultations
286 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More