It is estimated that 25% of the world’s population has some form of Nonalcoholic Fatty Liver Disease (NAFLD), a pathology associated with the development of cirrhosis, varices, and hepatocellular carcinoma. The discovery of a biallelic mutation in ABHD5 established the link between NAFLD and Chanarin-Dorfman syndrome. Consequently, it was hypothesized that additional NAFLD-inducing mutations could be associated with dermatologic manifestations.
International NAFLD patients from consanguineous families underwent whole exome sequencing. These results were then filtered by frequency and pathogenicity prediction algorithms (e.g. Mutation Taster, Polyphen, CADD) to yield novel mutations. Concurrently, a literature review via PubMed identified genes potentially involved in a mechanistic relationship between NAFLD and skin pathology.
In total, 72 unique genes with a possible mechanistic relationship between NAFLD and skin manifestations were identified in literature. The majority of these are involved in mitochondrial homeostasis, but some play a role in lipid droplet formation, insulin signaling, and intracellular transport. Genetic sequencing identified a causal ALMS1 mutation in the genotyped patient group.
While the identified mutation was not novel, it nonetheless provided an intriguing insight into NAFLD development and genetic diagnostics. Consolidating a proposed NAFLD-skin relationship between 72 genes helps strengthen the hypothesis of this relationship, and provides targets for future research and potential therapeutics.
Recommended CitationMedvedev, Anthony; Vahidnezhad, PhD, Hassan; Youssefian, PhD, Leila; and Uitto, MD, PhD, Jouni, "Establishing the Relationship Between Mendelian NAFLD and Skin Pathology" (2021). Phase 1. Paper 102.