Scientists have discovered a gene responsible for a devastating and life-threatening skin disease.
Hi-tech genetic analysis was used
The skin of babies with Harlequin Ichthyosis (HI) dries out to form hard diamond-shaped plaques, severely restricting their movement.
Most die soon after birth, but an increasing number are now surviving.
The research led by Queen Mary's School of Medicine and Dentistry in London, in the American Journal of Human Genetics, may lead to new treatments.
Research into the condition has proved difficult to carry out, largely because so few people with HI survive.
The Queen Mary team used a new technique called SNP array technology, which has made searching for disease genes a much quicker and cheaper process.
SNPs, or single nucleotide polymorphisms, are common, but minute, variations in the DNA sequence.
They occur when just one of the four letters that make up the code is out of place.
Identifying an SNP which is consistently inherited with a disease can help point researchers to the gene that may be ultimately responsible for the condition.
The researchers looked at individuals from 12 families affected by HI.
Using SNP array technology, they were able to pinpoint a suspect area of the genetic code linked to activity of a gene called ABCA 12.
Professor Kelsell hopes for a screening test
Further analysis revealed that 11 of the 12 patients in the study were carrying a mutated form of this gene.
HI is thought to be caused by a defect in the way lipids (fats) are transported and discharged into the top layers of the skin.
Normally, tiny spherical grains called lamellar granules migrate upwards through the skin, depositing lipids into the intercellular spaces of the skin's uppermost layer.
These lipids act as a protective barrier against bacteria and infection.
In patients with HI, these lamellar granules are not formed properly.
The researchers believe the ABCA12 gene may play a critical role in their formation.
Until now, pre-natal screening tests for HI have often been unreliable and inconclusive, involving risky, invasive procedures such as foetal skin biopsies.
Lead researcher Professor David Kelsell said: "The condition is extremely devastating, HI babies are in critical condition from birth being very susceptible to infection and other complications - the reason why many die.
"A key problem is that the disease is inherited in a recessive manner, so, if there is no previous HI child in the family, the appearance of an HI baby is shocking and unexpected to parents and the clinicians dealing with the birth."
He said that with excellent intensive care, HI babies could survive.
There are HI children in their late teens living life as normally as possible with their condition.
"By identifying ABCA12, our team has provided the molecular clue towards understanding the numerous biological abnormalities seen in HI skin," Professor Kelsell said.
Potentially this could lead not only to a new test to detect the condition at an early stage of pregnancy, but also to new treatments, including gene therapy and skin creams, which could replace the deficient lipids.
Professor Leonard Milstone, vice-president of the Foundation for Ichthyosis & Related Skin Types in the US, said the research was "a very nice piece of work with significant clinical implications".
"First, it will permit rational family planning for families already affected by this difficult problem.
"Second, once the function of this gene is described, new, logical, molecularly-targeted approaches to therapy become possible."