A study led by researchers at the Imperial College London in the United Kingdom recently reported the finding of a new inherited genetic defect that causes type 2 diabetes and obesity in humans. The study was published in the journal PLoS One and is entitled “Truncating Homozygous Mutation of Carboxypeptidase E (CPE) in a Morbidly Obese Female with Type 2 Diabetes Mellitus, Intellectual Disability and Hypogonadotrophic Hypogonadism.”
Genetic diseases are caused by one or more defects in the patient’s genome, and they may or may not be heritable from the individual’s parents. Several genes play a crucial role in various cellular mechanisms and biological processes in the body, including the regulation of body weight. Harmful mutations or alterations in around 30 specific genes have been reported in extremely obese individuals. Defects in a number of genes have also been found in type 2 diabetes patients. However, it is not clear which proportion of severe obesity and type 2 diabetes cases is caused by genetic disorders.
“There are now an increasing number of single-gene causes of obesity and diabetes known. We don’t know how many more have yet to be discovered, or what proportion of the severely obese people in our population have these diseases — it is not possible to tell just by looking,” explained the study’s senior author Dr. Alexandra Blakemore in a news release. “These are serious disorders that affect the body’s ability to regulate hunger and fullness signals. They are inherited in the just 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 study, researchers analyzed a particular case of an extremely obese young Sudanese woman who had severe weight problems since childhood, learning difficulties, reproductive problems and also type 2 diabetes. Members of the patient’s family were also assessed.
The patient was evaluated by Dr. Tony Goldstone, an endocrinologist at Hammersmith Hospital. The team reported that the parents of the patient were cousins and that she had an older brother with similar clinical symptoms who died with 21 years.
DNA sequencing revealed that the patient had inherited from her parents two copies of a deleterious genetic alteration that resulted in an inability to produce a protein called carboxypeptidase-E (CPE). CPE is an enzyme important for the proper processing of several hormones and brain transmitters that control appetite, insulin levels and the reproductive system. Previous studies in mice showed that CPE deletion results in diabetes, obesity, memory deficits, infertility, anxiety and depression. However, the condition of CPE deficiency had never been reported in humans before.
“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 they are affected in more subtle ways that could increase their risk of obesity,” said the study’s lead co-author Dr. Suzanne Alsters.
The research team suggests that genetic tests should be performed in patients with severe obesity. “If people are diagnosed with a genetic condition like this one, we can look for other possible symptoms, and offer genetic advice to other family members if they want this. Diagnosis is very valuable to the patient. It helps to set realistic expectations, and can help them get the best possible treatment,” concluded Dr. Blakemore.