About Careers MedBlog Contact us

Genetic Mutations Linked to Non-alcoholic Fatty Liver Disease Discovered

by Colleen Fleiss on July 28, 2019 at 5:59 PM
Font : A-A+

Genetic Mutations Linked to Non-alcoholic Fatty Liver Disease Discovered

Mutations in ABHD5 gene associated with non-alcoholic fatty liver disease have been reported by researchers led by Jouni Uitto, MD, PhD, Professor of Dermatology and Cutaneous Biology at Thomas Jefferson University. The finding provides a genetic basis for the condition.

Fatty liver disease is often associated with alcoholism, but more than a third of Americans have fatty livers despite moderate or absent alcohol consumption. They suffer from non-alcoholic fatty liver disease, a condition that can lead to cirrhosis, liver cancer and liver failure. Many patients require liver transplants to beat the disorder.


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.

The research shows the value of studying rare diseases, conditions in which there are less than 200,000 affected individuals in the U.S. The researchers were able to make the connection between cases of non-alcoholic fatty liver disease and the skin disorder Chanarin-Dorfman syndrome because they study a rare disease.

"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.

Additionally, "the link between non-alcoholic fatty liver disease and scaly skin diseases such as Chanarin-Dorfman syndrome highlights the importance of regulated lipid metabolism in skin physiology," says Dr. Uitto. "In fact, there are several heritable disorders manifesting with dry and scaly skin associated with mutations in genes like ABHD5 that are involved in lipid metabolism. Identification of such genes and specific mutations now form the basis for ongoing studies attempting to develop treatment for these often devastating skin disorders."

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, edyta.zielinska@jefferson.edu.

Source: Newswise


Recommended Reading

Latest Genetics & Stem Cells News

 Stem Cell Treatment Resolves Perianal Fistulas in Crohn's Disease
Can stem cell therapy cure fistula? Yes, treatment with stem cells has had a success rate when used in perianal fistulas due to Crohn's Disease.
First Effective Preclinical Models for Most Common Genetic Cause of Leigh Syndrome
In zebrafish models of SURF1 mitochondrial disease, scientists have discovered drugs to prevent neurological decompensation.
Gene Therapy for Rare Eye Disease
New study advances intravitreal gene therapy platform to develop safe and effective therapies for visual loss in Usher Syndrome, rare disorder.
Autism-associated Mutation: New Insights
The study experiments shed light on a rare example of how autism-associated mutation could altered nuclear dynamics.
How Genomic Variants Could Help Diagnose Rare Genetic Disorders
A genotype-first approach to patient care involves selecting patients with specific genomic variants and then studying their traits and symptoms.
View All
This site uses cookies to deliver our services.By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use  Ok, Got it. Close

Genetic Mutations Linked to Non-alcoholic Fatty Liver Disease Discovered Personalised Printable Document (PDF)

Please complete this form and we'll send you a personalised information that is requested

You may use this for your own reference or forward it to your friends.

Please use the information prudently. If you are not a medical doctor please remember to consult your healthcare provider as this information is not a substitute for professional advice.

Name *

Email Address *

Country *

Areas of Interests