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Identification of a Variant in APOB Gene as a Major Cause of Hypobetalipoproteinemia in Lebanese Families.
Ayoub, Carine; Azar, Yara; Abou-Khalil, Yara; Ghaleb, Youmna; Elbitar, Sandy; Halaby, Georges; Jambart, Selim; Gannagé-Yared, Marie-Hélène; Yaghi, Cesar; Saade Riachy, Carole; El Khoury, Ralph; Rabès, Jean-Pierre; Varret, Mathilde; Boileau, Catherine; El Khoury, Petra; Abifadel, Marianne.
Afiliación
  • Ayoub C; Laboratory of Biochemistry and Molecular Therapeutics (LBTM), Faculty of Pharmacy, Pôle Technologie-Santé, Saint Joseph University of Beirut, Beirut 17-5208, Lebanon.
  • Azar Y; Laboratory of Biochemistry and Molecular Therapeutics (LBTM), Faculty of Pharmacy, Pôle Technologie-Santé, Saint Joseph University of Beirut, Beirut 17-5208, Lebanon.
  • Abou-Khalil Y; Laboratory for Vascular Translational Science (LVTS), INSERM U1148, Bichat Hospital, F-75018 Paris, France.
  • Ghaleb Y; Centre Hospitalo-Universitaire Xavier Bichat, Université de Paris, F-75018 Paris, France.
  • Elbitar S; Laboratory of Biochemistry and Molecular Therapeutics (LBTM), Faculty of Pharmacy, Pôle Technologie-Santé, Saint Joseph University of Beirut, Beirut 17-5208, Lebanon.
  • Halaby G; Laboratory for Vascular Translational Science (LVTS), INSERM U1148, Bichat Hospital, F-75018 Paris, France.
  • Jambart S; Centre Hospitalo-Universitaire Xavier Bichat, Université de Paris, F-75018 Paris, France.
  • Gannagé-Yared MH; Laboratory of Biochemistry and Molecular Therapeutics (LBTM), Faculty of Pharmacy, Pôle Technologie-Santé, Saint Joseph University of Beirut, Beirut 17-5208, Lebanon.
  • Yaghi C; Laboratory for Vascular Translational Science (LVTS), INSERM U1148, Bichat Hospital, F-75018 Paris, France.
  • Saade Riachy C; Laboratory of Biochemistry and Molecular Therapeutics (LBTM), Faculty of Pharmacy, Pôle Technologie-Santé, Saint Joseph University of Beirut, Beirut 17-5208, Lebanon.
  • El Khoury R; Laboratory for Vascular Translational Science (LVTS), INSERM U1148, Bichat Hospital, F-75018 Paris, France.
  • Rabès JP; Faculty of Medicine, Saint Joseph University of Beirut, Beirut 17-5208, Lebanon.
  • Varret M; Faculty of Medicine, Saint Joseph University of Beirut, Beirut 17-5208, Lebanon.
  • Boileau C; Faculty of Medicine, Saint Joseph University of Beirut, Beirut 17-5208, Lebanon.
  • El Khoury P; Hotel Dieu de France of Beirut University Hospital, Beirut 166830, Lebanon.
  • Abifadel M; Faculty of Medicine, Saint Joseph University of Beirut, Beirut 17-5208, Lebanon.
Metabolites ; 11(9)2021 Aug 24.
Article en En | MEDLINE | ID: mdl-34564380
Familial hypobetalipoproteinemia (FHBL) is a codominant genetic disorder characterized by reduced plasma levels of low-density lipoprotein cholesterol and apolipoprotein B. To our knowledge, no study on FHBL in Lebanon and the Middle East region has been reported. Therefore, we conducted genetic studies in unrelated families and probands of Lebanese origin presenting with FHBL, in order to identify the causes of this disease. We found that 71% of the recruited probands and their affected relatives were heterozygous for the p.(Arg490Trp) variant in the APOB gene. Haplotype analysis showed that these patients presented the same mutant haplotype. Moreover, there was a decrease in plasma levels of PCSK9 in affected individuals compared to the non-affected and a significant positive correlation between circulating PCSK9 and ApoB levels in all studied probands and their family members. Some of the p.(Arg490Trp) carriers suffered from diabetes, hepatic steatosis or neurological problems. In conclusion, the p.(Arg490Trp) pathogenic variant seems a cause of FHBL in patients from Lebanese origin, accounting for approximately 70% of the probands with FHBL presumably as a result of a founder mutation in Lebanon. This study is crucial to guide the early diagnosis, management and prevention of the associated complications of this disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Screening_studies Idioma: En Revista: Metabolites Año: 2021 Tipo del documento: Article País de afiliación: Líbano Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Screening_studies Idioma: En Revista: Metabolites Año: 2021 Tipo del documento: Article País de afiliación: Líbano Pais de publicación: Suiza