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Removing guilt: the relief of a diagnosis For families with a child born with a neurodevelopmental condition, it’s hard not to wonder: was this already written in our genes? Professor Louise Bicknell is a geneticist at the University of Otago who has helped more than 300 families around the world find a genetic diagnosis for their child’s condition. Her focus is on rare neurodevelopmental diseases, many of which are caused by changes in a single gene. These conditions often affect brain growth and function, leading to developmental delay, intellectual disability and epilepsy. The underlying cause, or even a name for the disease, is often unknown or only partially understood. “For many families, it’s the first time they’ve had an explanation for what is happening,” Louise says. “It can remove a lot of guilt and provide a clearer picture of what the future might hold.” Louise and her team recently completed a Neurological Foundation–funded project, using advances in DNA sequencing and computing to study both children and adults in New Zealand families affected by neurodevelopmental conditions. The team identified several clear genetic causes, including newly described and rare gene changes. One example is an adult who was finally given a diagnosis of Strømme syndrome. They had microcephaly (a significantly smaller head size) along with developmental delay and a rare liver disorder called biliary atresia. Genetic testing revealed changes in both copies of the CENPF gene, confirming the diagnosis. Louise has been funded by the Neurological Foundation since 2018 through three successive project grants, allowing the research to maintain momentum, keep pace with advancing technology, and continue enrolling new families. In one of these earlier studies Louise’s teammade a major breakthrough, identifying genetic alterations in a gene called CRNKL1 as the cause of a severe neurodevelopmental disorder affecting brain growth. This work was published in one of the top genetics journals, American Journal of Human Genetics , which won Louise and her team the Faculty publication of the year prize in 2025. Teammember Dr Sankalita Ray Das presented this work at the hotly contested Otago Medical School Research Society Staff Research Award, winning the competition. Through international collaboration, the team has now found eight families worldwide (including one in New Zealand) with changes in this gene, confirming its role in disrupting brain development. In 2024, Louise received a travel grant from the Neurological Foundation to present these findings in Berlin at the European Society of Human Genetics Annual Meeting, one of the leading conferences in medical genetics, attended by around 4,000 researchers from around the world. Only 5%of attendees were selected to present their findings. “Europe is one of the most advanced and proactive regions for medical genetics, and many of our collaborators are based there,” she says. Given the rarity of these disorders, Louise says global collaboration is essential. “We simply wouldn’t be able to make these discoveries if we were working in isolation.” However, Louise says it is important to keep whole genome sequencing in New Zealand to support timely analysis and ensure genetic data is managed in line with expectations around data sovereignty, particularly for Māori. The work is also supporting the next generation of Kiwi researchers. Last year both Sankalita and Dr Meghan Mulligan in Louise’s teamwere awarded First Fellowships, and Honours student Ria Knoef was awarded a Doctoral Scholarship, starting her PhD in April. Ria is working with a New Zealand family whose genetic variants have been associated with a neurodevelopmental disorder called Coffin-Siris syndrome (CSS). Sankalita is extending findings from CRNKL1 to other proteins and is working with three families (five affected individuals) where alterations have been found in the spliceosome, which is an essential part of our cells for producing proteins. Her remarkable study will involve growing human brain cells in the lab to mimic these gene changes, helping her to understand whether the alterations are the underlying cause of neurodevelopmental disorders. Dr Meghan Mulligan’s fellowship extends from her involvement in an international collaboration during her PhD that helped to identify a new cause of a neurodevelopmental condition. She is now focusing on two other similar genes, using advanced cell models to study genetic alterations identified in her international patient cohort, aiming to confirm the roles of these genes in neurodevelopmental conditions. Louise says any research that can provide more information to families is invaluable. “Through the formal identification of a genetic cause, families can receive more personalised information about wellbeing for their child, what the future might hold, risks for other family members, and further support and therapy,” Louise says. “There are always new families being enrolled into our study, and therefore we appreciate the support to be able to study and help these families. Most of our findings are immediately translatable in that they can be returned, via the clinician, to the family.” This important research is made possible through the kindness and generosity of The A B de Lautour Charitable Trust and Southerly46 Trust. Louise personally extends her heartfelt thanks to the supporters who have significantly contributed to her research. Louise with her research team. Louise with PhD student Ria Knoef (left), Dr Sankalita Ray Das (front) and Dr Meghan Mulligan (right). Professor Louise Bicknell in her laboratory at the University of Otago. A spokesperson for Southerly46 Trust says: “We feel privileged to support Louise’s research and are impressed by the calibre and impact of her team, who are getting international recognition. We love the focus on benefitting families and children – the insights that stem from Louise’s research will undoubtedly be invaluable to the families involved.” 18 Headlines 19 Headlines