Inherited Non-Alcoholic Fatty Liver Disease and Dyslipidemia Due to Monoallelic Abhd5 Mutations Publisher Pubmed



Youssefian L^{1, 2, 3} ; Vahidnezhad H^{1, 4} ; Saeidian AH¹ ; Pajouhanfar S¹ ; Sotoudeh S⁵ ; Mansouri P⁶ ; Amirkashani D⁷ ; Zeinali S^{4, 8} ; Levine MA⁹ ; Peris K^{10, 11} ; Colombo R^{11, 12} ; Uitto J¹
Source: Journal of Hepatology Published:2019

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. © 2019 European Association for the Study of the Liver