Imprinting Disorders And Assisted Reproduction Techniques -- World's Largest Study Results Are Reassuring

Genetic imprinting is a mechanism in which gene expression depends upon parental origin. Mutations can alter normal imprinting, thus causing genetic abnormalities. Beckwith-Widermann syndrome (BWS) , Transient Neonatal Diabetes (TND), and Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are all acquired because of either a maternal or paternal deletion on a chromosome or from inheritance of both chromosomes of a pair from one parent.

"It has been known for some time that BWS, for example, was associated with ART", said Dr. Sutcliffe, "and we set out to look at the association of all four disorders and assisted conception." Dr. Sutcliffe and his team contacted patients throughout the UK who were in support groups for the disorders and obtained family histories and details of whether or not they had had ART, and if so, which kind. Out of 82 replies from families who had had a child with BWS, 10 had used ART in order to conceive (12%). Families with children with TND, AS, and PWS were also contacted and asked the same questions.

"We found that BWS was the only disorder where there was a significant risk for children conceived by ART", said Dr. Sutcliffe. "However, we found that all affected children apart from those with BWS had a mixture of genomic mutations, whereas those with BWS had a suggested mechanism -- maternal loss of methylation". Methylation is a mechanism used to inactivate parts of a chromosome to prevent problems.

Dr. Sutcliffe says that his findings are encouraging. "Not only have we found a possible mechanism for the occurrence of BWS, but we found no significantly higher rate of any disorder in children born after ART apart from BWS. Neither did we find that any particular method of ART was implicated. The problem with BWS could be in the culture media, or it could simply be that the parents are naturally infertile because of a genetic abnormalities.

"We are now planning to do a further study on the childhood eye cancer, retinoblastoma, where it is believed that imprinting is involved. What would help us enormously would be in the UK Human Fertilisation and Embryology Authority and the cancer registries were to link their databases to enable us to study this condition", he said.

Although such disorders are unusual, said Dr. Sutcliffe, "to a parent a child with a rare disorder, this is irrelevant. They simply have a sick child, and it is just as important for us to try and find treatments and cures for these conditions as for those that are more common."