A new approach to genetic testing funded by the IHC Foundation has provided diagnoses of rare genetic conditions for 11 New Zealand families so far, with more positive results expected from a pilot programme.
A research team, led by Professor Russell Snell, Dr Jessie Jacobsen and Associate Professor Klaus Lehnert at the University of Auckland, used the latest genome sequencing technology to look for a genetic diagnosis for children with undiagnosed, rare neurodevelopmental disorders.
Twenty families from throughout New Zealand participated in a two-year pilot study to discover the genes responsible for disorders that couldn’t be explained through standard tests. The team hoped to provide answers for at least 10 of the 20 families but the results are even more encouraging.
Of the 20 families, researchers discovered the gene or mutation responsible for the condition in 11 individuals. These results will now be confirmed by a diagnostic laboratory and clinicians will discuss treatment options and other implications with the families.
The results from a further seven families are still being analysed but Russell says he is optimistic that they will be able to provide a diagnosis for at least half of these families.
Researchers were not able to provide a diagnosis for two families, but Jessie says the team has no plans to give up and will now look for more complex causes. She says they will look for things like deletions or duplications or more complex breaks in the chromosomal material.
“Sometimes I underestimate how brilliant it is to be able to provide a family with a diagnosis. Having an answer can be a real relief for the family,” she says. For families dealing with very rare conditions, it means they can connect with others elsewhere in the world for support and to share information. For others it will mean the end of a long ‘diagnostic odyssey’ to get an answer, or to know whether or not it is an inherited condition.
Russell says the team is achieving results with their streamlined sequencing process as good, if not better, than anywhere else in the world. “We are quite good at this. Most people use a simplified process that struggles to discover the very rare disorders.”
He says their process is more cost-effective than standard tests that screen gene by gene. The team sequences the whole genome of the affected individual but only 1 percent of the DNA (the exome) of the parents. Sequencing the exome – the protein-coding regions – is about half the cost of sequencing the genome. The exome is thought to harbour about 85 percent of DNA variations that cause disease. Their aim is to provide evidence to the Ministry of Health that this is the best clinical approach to genetic testing.
“It will simplify clinical genetics in the broader sense. If you do what we are doing you can replace all the clinical genetic tests with this single test – that is, sequence the genome and evaluate that. Because it’s simpler it will be more efficient and it will be cheaper in the long run. “It is of course hugely dependent on having biology experts with computer skills who can relate findings to the biology and we are very fortunate in having Klaus in our team.”
Former IHC Foundation Chair Sir Roderick Deane says the result of the research is great news. “I cannot tell you how pleased I am with the quality of this work and its outcomes. For parents to know what the problem is becomes hugely important to the families. “In the case of my wife Gillian and me, very many years ago, we did not know about our daughter Kristen having Rett syndrome until she was well into her teens. It was an agony not understanding.
“Some so-called specialists had the gall to tell us it was our ‘fault’ and others totally misled us with wrong diagnoses. In contrast, other medical people were marvellously supportive but did not know what the problem was. Then the specialist in the United States whom we saw wrote to us after we had returned to New Zealand and said she had just heard Andreas Rett talk at a conference and she immediately knew she had a patient with the syndrome. Even today, it moves me to think about it and what that information meant to us.”
Dr Juliet Taylor, Clinical Geneticist at Genetic Health Service New Zealand, says without this research many of the families would not have had access to the type of genetic testing that had the great chance of making a diagnosis. “The benefits of getting a diagnosis for these families are immense and include changes in medical management and/or reproductive options becoming available. Just as important, these families find out the reason why, and the benefit of this, for parents in particular, can never be discounted even many years after the birth of a child.”
The IHC Foundation funded the $147,000 cost of collecting and reading the DNA.