Opening new genetic windows on diagnosis

Women make up the majority of the Molecular Genetics team at the National Centre for Medical Genetics in Dublin – 22 of the 25-strong team are female. Claire O’Connell finds out from Dr Aileen Butler how mining into genes can help patients get the right treatment.

Sometimes, inherited medical conditions can be hard to diagnose from symptoms alone. But in many cases, genetic testing can bring things into sharper focus, by ruling conditions out or offering a definitive diagnosis. For some patients, knowing that specific part of their genetic makeup can even guide them to the most appropriate treatment.

Since the 1990s, the National Centre for Medical Genetics (NCMG) at Our Lady’s Children’s Hospital, Crumlin, has been examining patient samples, and today it offers access to hundreds of genetic tests for specific conditions and holds a wealth of clinical information about genetic disease in Ireland.

Genetic explosion

The field of genetic testing has exploded in recent years, thanks to new technologies, data handling capacity and the identification of genes linked to disease, explains Dr Aileen Butler, principal clinical molecular geneticist with the division of Molecular Genetics at the NCMG.

During her career, she has witnessed the growth first hand. After studying zoology at University College Cork she moved to Trinity College Dublin, where for her PhD in the 1990s she looked at genes involved in the immune response. At that stage, the technology was relatively hard labour for slow gain.

“The amount of time and work involved was massive, and the computer programming to put the information together was very basic at the time,” explains Butler. “Today, somebody can generate the sequence of a whole genome for multiple individuals in the amount of time it took me to sequence just one gene. Also the pace of discovery of single genes that are associated with specific inherited disorders has been exponential in the time since I was in college.”

Mission: diagnosis 

Having the relevant genetic information from a patient sample can help to resolve a diagnosis, or at least rule particular conditions out. “Previously, maybe you had multiple diagnoses rather than being able to say for sure what is going on,” says Butler. “It gives you the confidence to confirm diagnosis, and with it a multitude of benefits for patients and their families.”

One of the most common queries they deal with at the NCMG is for Fragile-X, she explains. “That is a test for a gene that underlies a certain proportion of developmental delay and intellectual impairment issues,” says Butler. 

While many queries come in for Fragile-X, only around 1pc test positive but having that information is important for the child and family, she notes. “Where a diagnosis is made, it is so important – it means the risk within the family is highly significant, and we can give information about recurrence or the risk of someone else in the family developing associated symptoms in the future.”

Another common query is to test for genetic mutations associated with cystic fibrosis. “Ireland has the highest carrier incidence [for the genetic mutations] and the highest prevalence so the numbers of query diagnoses would be relatively high,” says Butler.

Since 2011, cystic fibrosis has been included in the ‘heel prick’ screening test for newborns in Ireland, so the numbers of queries coming in has been increasing, she adds.

“Now we have the opportunity of diagnosing children who will be affected very early, and that can make a difference in terms of quality of life, life expectancy and appropriate clinical management,” she says. “Literally within weeks of birth they can get the treatment they need.”

The centre offers diagnostic testing for a range of other genetic disorders, too, according to Butler, and refers to other labs internationally for 500 to 600 other rare conditions. “We work with networks of other diagnostics labs worldwide,” she explains.

Then when a person gets a diagnosis, clinical geneticists and genetic counsellors at the NCMG can work with patients and their families to address questions and concerns, she adds. “We are an integrated unit.”

Constant updating

Because the pace of diagnostic genetic testing advances so quickly, diagnostic labs around the world are kept on their toes, and the NCMG is no exception, says Butler. “There’s a challenge there, but we have a highly skilled staff base, and we can train up on the new technologies.”

Getting capital funding is key in this area, she adds. “That is a common need in many areas of medicine, but the particular challenge for us is that the whole field is moving on very quickly.”

The centre, which receives funding through the HSE and also patient charities, is now looking to establish next-generation sequencing (NGS) technologies that stand to offer more benefits to patients, according to Butler.

“Many technologies or tests only interrogate specific genes, but NGS gives you a broader scope, you could look at 10 or 20 genes all at the one time,” she explains. “For rare diseases and conditions like cancer that have a lot of genes involved, the benefits are massive.”

As well as the need for capital investment, the centre also faces the challenges of a rising demand for diagnostic testing “without proportionate increase in capital and day-to-day budget and in the face of severe staffing restrictions”, notes Butler.

“[Staff are] highly qualified specialists in their area, many being the only person delivering genetic testing for a particular disease in the country,” she says. “There is a vast knowledge and vast database here in terms of the needs of the Irish population. We want to be a key part of the planning in the health service going forward.”

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