Rare gene mutation blamed for some childhood obesity

A rare genetic mutation may explain the weight of some severely overweight young children, a study has found. The new findings have already affected when social workers judge children to be deliberately overfed or neglected.

British researchers compared the DNA of 300 children who developed severe obesity before 10 years old with more than 7,000 apparently healthy volunteers. Five children were missing DNA from chromosome 16, including SH2B1 - a gene involved in weight regulation and blood sugar control. The study, which was published online in the journal Nature on 6 December 2009, may be the first to show this type of genetic deletion can cause obesity.

Sadaf Farooqi, a lead researcher on the study said: 'Our results suggest that one particular gene on chromosome 16 called SH2B1 plays a key role in regulating weight and also in handling blood sugar levels. People with deletions involving this gene had a strong drive to eat and gained weight very easily'.

Four of the five children were considered by social workers to be at risk of abuse, according to a report in The Times newspaper. 'We found five children with this deletion, and when we got in touch with their families with the results we found four had been put on the at-risk register', said Dr Farooqi, adding: 'We're at various stages of discussion with social services. Two of the children have already been taken off the register and we're optimistic about the other two cases'.

Dr Farooqi, Matt Hurles from the Wellcome Trust Sanger Institute, and their colleagues scanned the children's DNA for mutations in copy number variations (CNVs). These are sections of DNA that vary in length between people, meaning they can have different numbers of genes. Too many or missing genes are a hallmark of many genetic diseases. 'We identified several rare copy number variants that were recurrent in patients but absent or at much lower prevalence in controls', said Dr Farooqi.

'This is the first evidence that copy number variants have been linked to a metabolic condition such as obesity. They are already known to cause other disorders such as autism and learning difficulties', Dr Hurles said.

The findings have implications for how severely obese children are diagnosed and when social services should intervene to protect them from abuse. Obesity is a factor in about 20 child-protection cases each year, according to surveys cited in The Times. In 2007, an eight-year-old girl was taken into care by Cumbria County Council over weight-related health fears. According to Dr Farooqi, the study: 'adds to the growing weight of evidence that a wide range of genetic variants can produce a strong drive to eat'. He hopes the team's findings will change 'attitudes and practices amongst those with professional responsibility for the health and well-being of children.'