by Gopalan on  May 12, 2008 at 10:20 AM Research News
Mutated Gene Behind Epilepsy and Mental Retardation Identified in Women
Anglo-Australian researchers say they have found a mutated gene linked with epilepsy and mental retardation in women.

It is hoped the findings could lead to prenatal screenings.

Senior medical scientist at Adelaide's Women's and Children's Hospital Leanne Dibbens said the findings could open up new research areas that would benefit hundreds of thousands of epilepsy sufferers and people with intellectual disabilities.

Dr Dibbens says the hereditary condition specific to women is rare but has been known to affect successive generations, ABC News reports.

"We do have two families here in South Australia which suffer from the disease but within those families there are many affected females and there are males who can pass on the gene and not know it until now," she said.

"It offers them tremendous potential in trying to avoid having children, or girls, with this nasty disease as we can now offer them genetic counselling and prenatal diagnosis.

"And for the wider community it will lead to new research into the genes that are involved in epilepsy and intellectual disability."

A rare condition called epilepsy and mental retardation limited to females (EFMR), which leads to seizures from infancy or early childhood and cognitive impairment, is caused when women inherit a defective copy of the PCDH19 gene, says Mark Henderson, Science Editor of Britain's Times Online.

The discovery is surprising because the PCDH19 gene is on the X chromosome, and genetic mutations on this chromosome usually cause disease only among males.

Females have two copies of the X chromosome, which generally protects them against X-linked mutations because they have a healthy back-up that can compensate. While they can be carriers of genetic conditions and pass them to their children, they do not normally fall ill themselves.

As males have only one X chromosome and Y chromosome, they have no back-up for genetic errors on the X, which can thus trigger severe diseases such as Duchenne muscular dystrophy and haemophilia.

The PCDH19 mutation, discovered by an international team led by Leanne Dibbins of the University of Adelaide, reverses this usual pattern.

The scientists, whose research is published in the journal Nature Genetics, suspect that the male Y chromosome may in some way be capable of compensating for the damage to the X, while the second female X chromosome cannot.

Professor Mike Stratton, a member of the team from the Wellcome Trust Sanger Institute near Cambridge, said: "The way in which this unusual disease is caused, particularly why it is expressed in women rather than men, remains a puzzle, but we are one step closer to unravelling the story.

"Identification of PCDH19 as the underlying gene will now allow diagnostic testing in families with the disease opening the possibility of prevention of further cases."

One hypothesis is that the genetic damage that the mutation causes results in part from having a mixture of brain cells with defective and normal genes. In women, one copy of the X chromosome is randomly switched off in every cell, while in men, the same X is active in all of them.

Another strong possibility is that a gene found on the male Y chromosome, but not on the X, can compensate for the problems caused by the PCDH19 mutation. A good candidate is a related gene called PCDH11Y: while this has a similar counterpart on the X called PCDH11X, it is slightly different and may not work in quite the same way.

The findings emerged from a study of seven families from Australia, the United States, Israel and Ireland. In one family, 23 women across five generations have suffered from EFMR.

The results also point towards the PCDH family of genes as a promising area for further investigation of epilepsy and other brain conditions, including autism and obsessive-compulsive disorder.

"With 100 related proteins involved in this gene family, this study could lead to many new areas of research, with the need to understand the role and function of each protein," Dr Dibbens said.

Source: Medindia

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