Researchers may be a step closer to understanding the reasons behind a class of devastating birth abnormalities, thanks to a study published today in the journal Human Molecular Genetics.
A team of scientists led by Dr. Philip Stanier at Imperial College and Professor Andrew Copp at the Institute of Child Health, University College London, have identified a novel gene that provides the first information on the genetic basis of a severe form of spina bifida known as craniorachischisis.
Spina bifida is one of the commonest birth defects, affecting 1 in 1,000 pregnancies. At its most severe, it can result in stillbirth or death within a few hours or days of birth. In milder cases, babies may have limb paralysis and incontinence.
Spina bifida arises in the early stages of pregnancy when the part of the fetus that forms the brain and spinal cord, the neural tube, fails to close properly. The similarity of this closure process in mice and humans allowed the team to study the development of spina bifida in a naturally occurring mouse strain.
Dr. Philip Stanier from the Institute of Reproductive and Developmental Biology at Imperial College's Hammersmith campus said, "We have identified the gene that is mutated in the loop-tail strain of mice. These mice develop the severe form of spina bifida closely resembling that seen in humans."
"Although folic acid supplementation can reduce the occurrence of many cases of spina bifida, understanding the mode of action of the loop-tail gene may provide the key to identifying further therapies that will prevent this devastating disorder," he said.
Previous studies had identified the region on Chromosome 1 where the loop-tail gene was thought to be located. Using genetic analysis, a copy of the region's genomic sequence was created. Twelve candidate genes were identified, eleven of which were shown to be expressed during neural tube formation.
By comparing the genetic sequence of the genes in the loop-tail mouse with that of the normal mouse, a mutation in a newly identified gene, Lpp1, was revealed.
Professor Andrew Copp said: "Our identification of the loop-tail gene is a key finding which will aid in understanding the developmental pathway that regulates neural tube closure. The long term aim of our research is to develop new methods for preventing spina bifida, by treating the embryo as it develops during pregnancy."
The research was supported by grants from EBM Charitable Trust, SPARKS, the Welton Foundation, the Medical Research Council, the European Union, the Birth Defects Foundation, the Dunhill Medical Trust and the Wellcome Trust.
[Contact: Judith H. Moore, Stephen Cox ]