Inherited nonalcoholic fatty liver disease and dyslipidemia due to monoallelic ABHD5 mutations

Abstract Background and 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 has been no disclosure of the mendelian inheritance in NAFLD families. Methods We performed whole-exome or targeted next-generation sequencing on autosomal dominant NAFLD patients. 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 seven unrelated multiplex families encompassing 39 affected subjects. Conclusion We associate a mendelian form of NAFLD and/or dyslipidemia with monoallelic ABHD5 mutations. Lay Summary Nonalcoholic fatty liver disease (NAFLD) is a common multifactorial disorder with a strong genetic component. We have studied seven multiplex families with NAFLD and identified monoallelic mutations in the ABHD5 gene, defining mendelian inheritance with complete penetrance in individuals over 40 years of age. Thus, heterozygous mutations in ABHD5 are a risk factor for development of NAFLD.