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

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• 作者：Amandine Georges (1)
  Jessica Bonneau (2)
  Dominique Bonnefont-Rousselot (3)
  Jacqueline Champigneulle (4)
  Jean P Rabès (2) (8)
  Marianne Abifadel (2)
  Thomas Aparicio (5)
  Jean C Guenedet (4) (9)
  Eric Bruckert (6)
  Catherine Boileau (2) (8)
  Alain Morali (1)
  Mathilde Varret (2)
  Lawrence P Aggerbeck (7)
  Marie E Samson-Bouma (2)
  
• 刊名：Orphanet Journal of Rare Diseases
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：6
• 期：1
• 全文大小：2806KB
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• 作者单位：Amandine Georges (1)
  Jessica Bonneau (2)
  Dominique Bonnefont-Rousselot (3)
  Jacqueline Champigneulle (4)
  Jean P Rabès (2) (8)
  Marianne Abifadel (2)
  Thomas Aparicio (5)
  Jean C Guenedet (4) (9)
  Eric Bruckert (6)
  Catherine Boileau (2) (8)
  Alain Morali (1)
  Mathilde Varret (2)
  Lawrence P Aggerbeck (7)
  Marie E Samson-Bouma (2)
  
  1. Service de Médecine Infantile 3 et Génétique Clinique, INSERM U954, H?pital d’Enfants Brabois, CHU Nancy, Vandoeuvre les Nancy, 54511, France
  2. INSERM U781, Université Paris Descartes, H?pital Necker Enfants Malades, Paris, 75015, France
  3. UF de Biochimie des Maladies Métaboliques, Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière (AP-HP), and Département de Biologie Expérimentale, Métabolique et Clinique, EA 4466, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris, 75013, France
  4. Laboratoire d’Anatomie et de Cytologie Pathologiques, H?pital de Brabois, Université Paris 13, Bobigny, 93000, France
  8. Service de Biochimie et Génétique Moléculaire, CHU A Paré, AP-HP et Faculté de Médecine (PIFO-UVSQ), Boulogne, 92104, France
  5. Service de Gastroentérologie, H?pital Avicenne, 125 rue de Stalingrad, Université Paris 13, Bobigny, 93000, France
  9. Service de Microscopie Electronique, H?pital de Brabois, CHU Nancy, Vandoeuvre les Nancy, 54511, France
  6. Service d’Endocrinologie-Métabolisme, H?pital Pitié Salpêtrière, (AP-HP), Paris, 75013, France
  7. INSERM U747, Université Paris Descartes, Paris, 75006, France
  

文摘

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.