Scientists are aware of over 30 adverse mutations among genes involved in regulating body weight that are associated with obesity.
Scientists are aware of over 30 adverse mutations among genes involved in regulating body weight that are associated with obesity, as well as several gene alterations that are known to cause type 2 diabetes. Individuals with these genetic changes will inherit these conditions through their families.
"There are now an increasing number of single-gene causes of obesity and diabetes known," says Prof. Alex Blakemore, from the Department of Medicine at Imperial College London and leader of the new study.
Prof. Blakemore says that scientists do not know how many more of these genetic causes of obesity or diabetes remain to be discovered, or what proportion of severely obese people have them.
"These are serious disorders that affect the body's ability to regulate hunger and fullness signals," Prof. Blakemore continues. "They are inherited in just the same way as other genetic diseases and the sufferers should not be stigmatized for their condition. They should be offered genetic counseling and specialized lifelong support to allow them as healthy a life as possible."
In the new study, Prof. Blakemore and colleagues sequenced the genome of a young woman described as "extremely obese" and her family members. The woman had severe weight problems from childhood as a result of increased appetite, as well as type 2 diabetes, learning difficulties and problems with her reproductive system.
Analyzing the DNA sequencing, the team found that the woman had inherited two copies of a genetic mutation that prevented her body from making the protein carboxypeptidase-E (CPE). Several hormones and brain transmitters responsible for regulating appetite, insulin and hormones important in the reproductive system need CPE to function properly.
Although studies in mice have found an association between CPE deficiency and obesity, diabetes and memory problems, this condition had not previously been found in humans.
CPE deficiency only occurs when both parents have genetic alteration
CPE deficiency is a recessive condition, which means that both parents would need to have the altered genetic sequence for their offspring to be affected.
The parents of the woman in the study were cousins, which the researchers say gave the patient a higher likelihood of inheriting the same genetic change from both of her parents. An older brother of the patient had similar symptoms and died at the age of 21.
First author of the study Dr. Suzanne Alsters says:
"Finding a genetic cause for the patient's problems has helped her and her family to understand and manage her condition better. We can also look at members of her family with one abnormal copy of the gene, to see [if] they are affected in more subtle ways that could increase their risk of obesity."
Prof. Blakemore argues that genetic tests should be made widely available for people who are severely obese, so that doctors can offer genetic advice to family members. "Diagnosis is very valuable to the patient," Prof. Blakemore concludes. "It helps to set realistic expectations, and can help them get the best possible treatment."