Inherited non-alcoholic fatty liver disease and dyslipidemia due to monoallelic ABHD5 mutations

[Display omitted] •Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world.•We identified monoallelic ABHD5 mutations in 7 families with NAFLD.•ABHD5 is involved in neutral lipid metabolism, highlighting the role of lipid disorders in NAFLD. 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. We performed whole-exome or targeted next-generation sequencing on patients with autosomal dominant NAFLD. 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. We associate a Mendelian form of NAFLD and/or dyslipidemia with monoallelic ABHD5 mutations. 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.