Strong Voices

The Sterne family has spent much of the past 21 years wondering whatever happened to Luke. Now, thanks to genetic researchers, they have the answer.

“When he was born I was a week overdue and he was severely growth-retarded, severely underweight,” says Luke’s mother Nicola Sterne.

Nicola was 33 when Luke was born in 2000, the Sternes’ second child. Nicola says she recalls feeling there was something wrong. “He was induced. It was a horrific time.”

She says an explanation from a doctor at Auckland’s National Women’s Hospital didn’t help. “She said, ‘He has an even chromosome translocation and we don’t know how that is going to manifest itself.’

“So I went home with this baby and literally went through six weeks of hell.” Luke wasn’t able to feed. “He wasn’t strong enough to swallow the formula. He was shaking because he was so malnourished,” Nicola says.

Luke was sent to Starship Hospital, where he was given the immediate help he needed. But as for what was actually wrong, no one knew. “His blood was sent to Germany and they couldn’t find anything wrong; they couldn’t find anything missing.”

Fast-forward to 2016, and Luke was recruited into a study being carried out by Minds for Minds genetic researchers at the University of Auckland’s School of Biological Sciences and Centre for Brain Research to find the genes and genetic variations responsible for rare conditions.

Luke’s younger brother Kyle recalls that it wasn’t plain sailing collecting blood from him. “I think they nearly gave up,” he says.

But it was an opportunity they couldn’t pass up. “It was so important for my other children to know,” Nicola says. And two years later they did, receiving a call from their clinical geneticist. “She said, ‘Well, it’s good news. He has a syndrome – DYRK1A’, a gene involved in brain development. Changes in the DYRK1A gene have been linked to intellectual disabilities, microcephaly, speech and language impairment, seizures and autism.

“It was a bit of a sad day because you know there is actually something wrong,” Nicola says. But it also provided some answers and certainty for the family.

Despite not knowing what had caused Luke’s disability, Nicola and husband Richard had a third child, Kyle. “I was determined to have another child, but Richard was hesitant. “I definitely felt I was taking a risk having another child.” Her third child Kyle was not affected. He is now at medical school and agrees that his choice of career may have something to do with the health issues faced by the family.

The same question about whether the disability might be inherited was faced by their daughter Sophie when it was her turn to have a family.

“My daughter is 25 and she had twins two and a half years ago. We were adamant that she was going to get tested. She had an amnio [amniocentesis – a test for a genetic or chromosomal condition],” Nicola says. Her granddaughter is named Zahra and grandson is Kais – “vibrant and very healthy children”.

Kyle says that having a diagnosis for Luke has not made any difference to him in terms of treatment, but it has answered other questions about life expectancy and what symptoms are related to the genetic condition. “There is a lot of power in knowing something, even if you can’t do anything about it,” he says.

What they now know is that the genetic change in the DYRK1A gene was not inherited in Luke’s case. “It’s called a first-generation mutation. It’s random,” Nicola says.

“I am deeply grateful because to get a genome [sequence and analysis] done is very, very costly.”

Nicola says Luke is limited in what he can do. “He can’t shower himself. He is able to go to a day programme, but only for two days. He loves the Sky Tower, he loves walking – he can walk 10 kilometres easily. He had a fantastic 21st.”

These days Nicola does her best to help other people to understand what it’s like, including talking to trainee nurses about her experiences with Luke.

“I would love to help any women in any way. It’s so hard, those first years. It’s so lonely,” she says. But looking back, she is grateful for the support of her family.

“Don’t think it can’t happen to you,” she says. “Life is not over, and you just have to do the best you can.

“This has happened. You can either sink or swim, and you have to do your best to swim. “You look at what you have achieved over 21 years and what you have achieved as a family. It’s hard though.”

University of Auckland researcher Dr Jessie Jacobsen leads the research project alongside Associate Professor Klaus Lehnert, Professor Russell Snell, and PhD student Chris Samson. They worked with colleagues at Massachusetts General Hospital and Harvard Medical School in Boston to resolve the complexities of the specific type of genetic rearrangement (a balanced rearrangement) observed in Luke’s DNA.

Jessie says one of the things that drives her is being able to provide answers for families. She says it is often harder to have a medical impact or intervention when a child is older, but even with older children, having a diagnosis gives the families an idea of what they can expect.

She says a balanced chromosomal rearrangement is a bit like rearranged chapters in books. “A balanced rearrangement is when you have whole chapters missing from one book (chromosome), but they reappear in another book (chromosome). As we don’t lose many of the words, just rearrange them, we often call this a balanced structural variant.”

Her research has been funded by the IHC Foundation. In the pilot project, from 2016 to 2018, the team conducted research with 20 families and was able to find the genes and mutations responsible for rare conditions in 14 children.

A second project, now nearly completed, aims, first of all, to provide answers for families to help manage the condition. Secondly, the results from these families could contribute significantly to evidence to support the use of this technology in mainstream clinical use. Thirdly, the gathering and cataloguing of naturally occurring genetic variations in the population will allow for a more efficient approach to identifying those genes that cause rare disorders.  “We are very grateful to the IHC Foundation for its help to help these families,” Jessie says.

Caption 1: The Sterne family is relieved to have some answers (from left) Patricia Alston (Luke’s grandma), Zahra, Nicola, Kyle, Luke, Sophie, and Richard holding Kais.

Caption 2: These days Nicola does her best to help other people to understand what it’s like to support Luke.

Caption 3: The cause of Luke Sterne’s disability was a first-generation genetic mutation.

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