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.
Keywords: ABHD5; CGI-58; Dyslipidemia; Familial aggregation; Inheritance; Mendelian; NAFLD; Non-alcoholic fatty liver disease.
Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.