Scientists have discovered a new
inherited form of obesity and type 2 diabetes in humans.
A large number of genes are
involved in regulating body weight, and there are now over 30 genes
known in which people with harmful changes in DNA sequence become
extremely overweight. Similarly, there are a number of genes that
can, when altered, cause type 2 diabetes. These conditions are
inherited through families in exactly the same way as disorders
such as cystic fibrosis or Huntington's disease.
It is unclear what proportion of
severe obesity and type 2 diabetes is caused by genetic
disease.
Researchers at Imperial College
London discovered the new defect by sequencing the DNA of an
extremely obese young woman and members of her family. In addition
to an increased appetite leading to severe weight problems from
childhood, she had type 2 diabetes, learning difficulties, and
reproductive problems.
They found that she had inherited
two copies of a harmful genetic change that meant she could not
make a protein called carboxypeptidase-E (CPE). This is an enzyme
that is important in the proper processing of a number of hormones
and brain transmitters controlling appetite, insulin and other
hormones important in the reproductive system.
Studies have previously shown that
CPE deficiency causes obesity, diabetes, and impaired memory in
mice, but no humans with the condition have been found before. CPE
deficiency is a recessive condition, so a person would need to
inherit the altered genetic sequence from both parents to be
affected.
Professor Alex Blakemore from
Imperial College London 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.
"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 stigmatised for their condition.
They should be offered genetic counselling and specialised lifelong
support to allow them as healthy a life as possible."
The patient was clinically
evaluated by consultant endocrinologist Dr Tony Goldstone, who runs
a specialist genetics obesity clinic at Hammersmith Hospital. The
patient's parents are cousins, giving her a relatively high
likelihood of inheriting the same genetic change from both parents.
She had an older brother with similar symptoms who died aged
21.
The first author Dr Sanne Alsters,
also at Imperial, said: "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."
Professor Blakemore said genetic
tests should be widely available for 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," she said.
The
paper, Truncating homozygous mutation of carboxypeptidase E (CPE) in a
morbidly obese female with type 2 diabetes mellitus, intellectual
disability and hypogonadotrophic
hypogonadism, is published
in PLOS One.