Jessie Jacobsen, Senior Lecturer, School of Biological Sciences and Centre for Brain Research, University of Auckland, Waipapa Taumata Rau, Suzanne Musgrave, Doctoral Candidate, School of Biological Sciences and Centre for Brain Research, University of A
A global rise in autism diagnoses is putting the spotlight on this relatively common neurodevelopmental difference. A recent study identified autism in 1.3% of four- to five-year-olds in Aotearoa New Zealand. This matches estimates overseas of 1% to 2% of eight-year-olds.
In our new research, we looked at how genetic testing could support how people in New Zealand are diagnosed.
Genetic screening of 201 autistic individuals, as well as 101 non-autistic family members, found almost 13% of autistic participants had a clearly identified genetic variant. An additional 16% had a DNA change that likely explained their autism.
Importantly, our analysis was successful in identifying autism-linked genetic variants for autistic New Zealanders regardless of neurological differences and other diagnoses such as ADHD. Many of these individuals were adults who grew up before autism was widely recognised.
Diagnosing autism
Autism affects cognitive, sensory and social processing. It can change the way people see the world and interact with others.
Autistic individuals may experience challenges with social communication and interaction. They may also have intense interests and a strong need for routines and predictability. These patterns of behaviour typically appear from childhood.
The challenge with diagnosing autism is that it often occurs along with other neurodevelopmental conditions or mental health challenges such as intellectual disability, ADHD, depression and anxiety.
An autism diagnosis typically involves meeting with an expert such as a developmental paediatrician or clinical psychologist. After diagnosis, some forms of genetic testing may be offered.
But there is interest in identifying the ever-growing genetic variations underlying autism to provide precise genetic answers for families.
For some, having a precise genetic answer marks the end of a long search for an accurate diagnosis. For others it has provided personalised clinical management for co-occurring conditions.
Having an accurate genetic answer can help people find community support. This personalised care can support an individual’s wide range of skills, interests and personalities.
A recent study from Canada found using genetic testing for the diagnosis of neurodevelopmental conditions can reduce time to diagnosis by more than half.
This has important implications for publicly-funded healthcare in Aotearoa New Zealand. But it also gives individuals and their families a chance to access support sooner and develop a tailored pathway of care for all aspects of their health needs.
Identifying the genetic variants
Our research participants ranged in age from two to 81, with a reported autism diagnosis. The majority were older children (six to 12 years). The participants had a wide range of neurological differences, reflecting the diversity of autistic individuals in New Zealand.
After collecting their DNA, we used a flexible genome-wide approach to screen the progressively expanding list of causative genes in autism.
Where we found variants in the DNA, we filtered them through key criteria: how often they appear in the population, the predicted consequence of the variant on protein function, and what role the gene has in neurodevelopment.
The variants were categorised as either “causal”, “likely causal” or a “candidate” (based on American College of Medical Genetics and Genomics guidelines and international databases such as the Simons Foundation Autism Research Initiative gene database).
Of our 201 research participants, 12.9% had a genetic variant identified as “causal”. A further 15.9% had variants defined as “likely causal”. An additional 13.9% had “candidate” variants, which require further evidence to establish their role in autism.
A “causal” or “likely causal” variant was more likely to be discovered in participants who also exhibited global developmental delay (when they are significantly delayed in two or more areas of development) or intellectual disability than those who did not.
Importantly, our genetic approach is successful for autistic individuals regardless of neurological differences.
Offering clarity
Our research demonstrates that comprehensive genome-wide genetic testing can provide precise genetic answers for individuals and their families, marking the end of a long search for an accurate diagnosis.
The genome-wide approach can enable expanded testing to newly discovered genes so participants can benefit without the need for repeated testing.
In addition to reducing costs in an already strained medical sector, genetic testing can offer clarity, and tailor customised support for autistic individuals and their families.
As one family explained:
A diagnosis is something we’ve never had and this has made it possible for us to understand so much more about why our daughter is like she is. It has been a big relief and helped us understand that issues we were aware of, such as hyper-mobility, are actually features of [the genetic variant] 2q37. It has enabled us to get further tests done for things specific to [this variant] such as potential heart defects and kidney conditions […] we are very grateful that this research has led to the diagnosis of [our daughter’s] condition.
Jessie Jacobsen has received funding from the Minds for Minds Charitable Trust, Cure Kids and A Better Start: E Tipu e Rea National Science Challenge, the IHC Foundation, Oakley Mental Health Research Foundation, The Neurological Foundation of New Zealand and a Rutherford Discovery Fellowship administered by the Royal Society Te Aparangi of New Zealand.
Suzanne Musgrave receives funding from the University of Auckland Doctoral Scholarship.
