Researchers identify gene tied to extremely rare disorder that causes inflammation and loss of fat

Dec 01, 2010

UT Southwestern Medical Center researchers have identified a gene responsible for a rare disease that results in severe joint stiffness, muscle loss, anemia and panniculitis-induced lipodystrophy, or JMP syndrome.

The researchers identified a blip in the gene – proteasome subunit, beta-type, 8 (PSMB8) – in three patients from two distinct families who were suffering from progressive loss of fat and muscles as well as joint contractures that particularly affected the hands and feet. The fat loss was due to recurrent inflammatory lesions under the skin called panniculitis. Lipodystrophies are disorders characterized by the selective loss of fat tissues and complications of insulin resistance.

Dr. Abhimanyu Garg, chief of nutrition and metabolic diseases and senior author of the study appearing online and in the Dec. 2 issue of The American Journal of Human Genetics, said that in addition to providing a clue to the cause of JMP syndrome, the findings also tell researchers more about the role proteasomes play in an individual's immune response. Although researchers identified proteasomes many years ago, their precise contribution to immunity in humans has eluded scientists.

"Our findings show that if this gene is mutated, it can lead to the development of an auto-inflammatory syndrome," Dr. Garg said. "How the mutation triggers is not entirely clear, but this does suggest new therapeutic targets for individuals with the condition."

The researchers used gene mapping technology on DNA samples of the study participants and their family members to find the PSMB8 gene. Two of the patients hailed from Monterrey, Mexico, and the third from Portugal.

They found that the mutation reduces activity of the PSMB8 enzyme within the immune cells and affects normal processing of antigens, resulting in inflammation.

The next step, Dr. Garg said, is to determine the best type of therapy and whether it is possible to prevent the disease or lessen the severity of some of its symptoms.

"This is a good start," Dr. Garg said. "There's more to be learned from the patients about the function of this immune-response gene."

Explore further: Down's chromosome cause genome-wide disruption

add to favorites email to friend print save as pdf

Related Stories

Fat-free diet reduces liver fat in fat-free mice

Feb 03, 2009

Researchers at UT Southwestern Medical Center have uncovered crucial clues about a paradoxical disease in which patients with no body fat develop many of the health complications usually found in obese people.

New gene linked to muscular dystrophy

Aug 10, 2009

Muscular dystrophy, a group of inherited diseases characterized by progressive skeletal muscle weakness, can be caused by mutations in any one of a number of genes. Another gene can now be added to this list, as Yukiko Hayashi ...

Recommended for you

Down's chromosome cause genome-wide disruption

7 hours ago

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

Research uncovers DNA looping damage tied to HPV cancer

13 hours ago

It's long been known that certain strains of human papillomavirus (HPV) cause cancer. Now, researchers at The Ohio State University have determined a new way that HPV might spark cancer development – by ...

New therapy against rare gene defects

Apr 15, 2014

On 15th April is the 1st International Pompe Disease Day, a campaign to raise awareness of this rare but severe gene defect. Pompe Disease is only one of more than 40 metabolic disorders that mainly affect children under ...

User comments : 0

More news stories

Down's chromosome cause genome-wide disruption

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

Simplicity is key to co-operative robots

A way of making hundreds—or even thousands—of tiny robots cluster to carry out tasks without using any memory or processing power has been developed by engineers at the University of Sheffield, UK.

Progress in the fight against quantum dissipation

(Phys.org) —Scientists at Yale have confirmed a 50-year-old, previously untested theoretical prediction in physics and improved the energy storage time of a quantum switch by several orders of magnitude. ...