Professor Alexandra Blakemore of Imperial College London and a lead author of the study, said: '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.'
In the study, published in PLOS ONE, the researchers analysed the genome of a young woman with morbid obesity and newly diagnosed type 2 diabetes. She also had a condition affecting her fertility and some learning difficulties. They used a shortcut called exome sequencing, which looks at just that one percent of a person's DNA that encodes proteins.
They found that the patient had inherited two mutated copies of the carboxypeptidase E (CPE) gene. The CPE protein is an enzyme that processes various hormones and chemical messengers called neuropeptides, which mice studies had previously shown to control appetite and insulin, among other roles.
Looking at the genomes of the patient's family who did not have the same symptoms, they also found that some close relations including her mother had one copy of the mutation. One of the patient's sisters, who had a single copy of the mutated CPE gene, was found to have lower levels of the CPE enzyme in her blood. The patient also had an older brother, who died aged 21 and who had shown similar symptoms.
The parents of the patient are first cousins, which increases the likelihood that two copies of a rare mutation such as this will be passed on.
The researchers noted previous research which showed that mice with mutations in the mouse equivalent of the CPE gene, or which had that gene removed, also developed obesity, infertility and disturbed insulin levels.
Type 2 diabetes is a condition in which the body does not produce enough insulin, or does not respond properly to insulin, leading to a dangerously high levels of glucose in the blood. Having a close relative with type 2 diabetes increases the risk of developing the condition, indicating that genetics is a significant factor.
The team is hopeful that knowing when conditions are caused by genetic factors will be helpful for patients. 'Finding a genetic cause for the patient's problems has helped her and her family to understand and manage her condition better,' said Dr Sanne Alsters, also of Imperial College, who carried out the genetic analysis. '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.'