Leila Youssefian1, Hassan Vahidnezhad2, Amir Hossein Saeidian3, Sara Pajouhanfar3, Soheila Sotoudeh4, Parvin Mansouri5, Davoud Amirkashani6, Sirous Zeinali7, Michael A Levine8, Ketty Peris9, Roberto Colombo10, Jouni Uitto11. 1. Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA; Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Genetics, Genomics and Cancer Biology PhD Program, Thomas Jefferson University, Philadelphia, PA, USA. 2. Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA; Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. 3. Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA. 4. Department of Dermatology, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 5. Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran. 6. Department of Pediatrics, Faculty of Medicine, Ali Asghar Children Hospital, Iran University of Medical Sciences, Tehran, Iran. 7. Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran; Kawsar Human Genetics Research Center, Tehran, Iran. 8. Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA. 9. Institute of Dermatology, Faculty of Medicine, Catholic University, Rome, Italy; IRCCS Policlinico Gemelli - University Hospital, Rome, Italy. 10. IRCCS Policlinico Gemelli - University Hospital, Rome, Italy; Institute of Clinical Biochemistry, Faculty of Medicine, Catholic University, Rome, Italy. Electronic address: roberto.colombo@unicatt.it. 11. Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: Jouni.Uitto@Jefferson.edu.
Abstract
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition and the most common liver disease worldwide, affecting more than one-third of the population. So far there have been no reports on mendelian inheritance in families with NAFLD. METHODS: We performed whole-exome or targeted next-generation sequencing on patients with autosomal dominant NAFLD. RESULTS: We report a heritable form of NAFLD and/or dyslipidemia due to monoallelic ABHD5 mutations, with complete clinical expression after the fourth decade of life, in 7 unrelated multiplex families encompassing 39 affected individuals. The prevalence of ABHD5-associated NAFLD was estimated to be 1 in 1,137 individuals in a normal population. CONCLUSION: We associate a Mendelian form of NAFLD and/or dyslipidemia with monoallelic ABHD5 mutations. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) is a common multifactorial disorder with a strong genetic component. Inherited forms of NAFLD have been suspected but, their molecular pathogenesis has not been disclosed. Here we report a heritable form of NAFLD with clinical expression after 40 years of age, associated with monoallelic ABHD5 mutations.
BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition and the most common liver disease worldwide, affecting more than one-third of the population. So far there have been no reports on mendelian inheritance in families with NAFLD. METHODS: We performed whole-exome or targeted next-generation sequencing on patients with autosomal dominant NAFLD. RESULTS: We report a heritable form of NAFLD and/or dyslipidemia due to monoallelic ABHD5 mutations, with complete clinical expression after the fourth decade of life, in 7 unrelated multiplex families encompassing 39 affected individuals. The prevalence of ABHD5-associated NAFLD was estimated to be 1 in 1,137 individuals in a normal population. CONCLUSION: We associate a Mendelian form of NAFLD and/or dyslipidemia with monoallelic ABHD5 mutations. LAY SUMMARY:Non-alcoholic fatty liver disease (NAFLD) is a common multifactorial disorder with a strong genetic component. Inherited forms of NAFLD have been suspected but, their molecular pathogenesis has not been disclosed. Here we report a heritable form of NAFLD with clinical expression after 40 years of age, associated with monoallelic ABHD5 mutations.
Authors: Richard K Sterling; Eduardo Lissen; Nathan Clumeck; Ricard Sola; Mendes Cassia Correa; Julio Montaner; Mark S Sulkowski; Francesca J Torriani; Doug T Dieterich; David L Thomas; Diethelm Messinger; Mark Nelson Journal: Hepatology Date: 2006-06 Impact factor: 17.425
Authors: C Lefèvre; F Jobard; F Caux; B Bouadjar; A Karaduman; R Heilig; H Lakhdar; A Wollenberg; J L Verret; J Weissenbach; M Ozgüc; M Lathrop; J F Prud'homme; J Fischer Journal: Am J Hum Genet Date: 2001-10-02 Impact factor: 11.025
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