Jefferson researchers unveil first demonstration of heritable mutations behind non-alcoholic fatty liver disease.

‘Patients with Chanarin-Dorfman syndrome develop dry, reddish and scaly skin shortly after birth. Later on in life, they acquire abnormally large and fatty livers. ’

The scientists made the discovery not by studying the liver, but the skin. Dr. Uitto and colleagues were investigating a condition called Chanarin-Dorfman syndrome, a severe but rare skin disorder, in several families from Iran. 




First author Leila Youssefian in Dr. Uitto’s lab, and others sequenced the genomes of six families. Several members of each family had non-alcoholic fatty liver disease, but didn’t have any skin symptoms. Although the researchers knew mutations in ABHD5 lead to Chanarin-Dorfman syndrome, the analysis helped to uncover a surprising link.
“It turns out that if you have one mutated copy of the ABHD5 gene you get the liver disease only,” say Dr. Uitto. “But, if you have mutations in both copies, then you get the liver disease plus Chanarin-Dorfman syndrome.”
The scientists confirmed the result by sequencing the genomes of members of a large Italian family with a family history of the liver disease. They found that the nine family members with non-alcoholic fatty liver disease had one mutated copy of the ABHD5 gene. The discovery indicates that mutations in one copy of ABHD5 predispose individuals to non-alcoholic fatty liver disease. The findings also suggest that parents of children with Chanarin-Dorfman syndrome should get screened for mutations in ABHD5.
Dr. Uitto and his team’s finding is the first demonstration of a heritable mutation that leads to non-alcoholic fatty liver disease, but further analyses revealed there are likely many more genes in addition to ABHD5 that underlie the condition.
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“Studying a rare, heritable disease such as Chanarin-Dorfman syndrome, can be very helpful in identifying conditions which are much more prevalent, like in the case of non-alcoholic fatty liver disease,” says Dr. Uitto.
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The researchers published their findings online in the Journal of Hepatology.
Article reference: Leila Youssefian, Hassan Vahidnezhad, Amir Hossein Saeidian, Sara Pajouhanfar, Soheila Sotoudeh, Parvin Mansouri, Davoud Amirkashani, Sirous Zeinali, Michael A. Levine, Ketty Peris, Roberto Colombo, and Jouni Uitto, “Inherited nonalcoholic fatty liver disease and dyslipidemia due to monoallelic ABHD5 mutations,” Journal of Hepatology, DOI: 10.1016/j.jhep.2019.03.026, 2019.
Media Contact: Edyta Zielinska, 215-955-7359, [email protected].
Source-Newswise