HOUSTON — For years, the parents of Owen Johnson carried a quiet conviction that autism diagnosis alone did not fully account for the complex mosaic of symptoms their son had exhibited since he was a toddler.
Owen was just three years old when he received an autism diagnosis. He had taken longer than expected to hit early milestones like speaking, and he struggled profoundly to connect with other children at his Houston preschool. Following the diagnosis, his pediatrician recommended a regime of early intervention therapies. While these interventions offered some initial progress, their effectiveness gradually plateaued. As the years passed, Owen’s parents watched an increasingly wide developmental gap open up between him and his twin sister, Alice.
"He had always been a very happy child in his early toddler years, and then he would just get so withdrawn," his mother, Jennifer Johnson, recalled, reflecting on the frustrating years of uncertainty. "I was really concerned."
Determined to find a deeper medical explanation, Owen’s parents sought a closer look into his biology. In 2021, his doctor ordered a blood sample to be sent out for comprehensive genetic testing. The family waited anxiously for answers, hoping science could illuminate the root cause of Owen’s developmental divergence. Instead, the results came back blank, revealing no actionable information or known genetic markers to explain his symptoms.
"It’s a helpless feeling," said his father, Dr. Peter Johnson, a neurologist who understands the limitations of diagnostic medicine firsthand. "If you don’t have an answer, then what can you do?"
Yet, across the city of Houston around that exact same time, a scientific breakthrough was quietly taking shape. Dr. Ryan Dhindsa and his laboratory team at the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital were investigating a suspicious, newly identified gene mutation while conducting broader research into Parkinson’s disease. Within months, Dhindsa’s lab would discover that this very same genetic anomaly was intimately connected to neurodevelopmental disorders like autism—and that it finally offered a clear, scientific explanation for Owen’s mysterious symptoms.
Searching for an Explanation
In his earliest years, Owen’s parents had no inkling that anything unusual was unfolding in his development. He began speaking later than typical children and developed intense fixations on specific things, such as the color red, but his family initially chalked these traits up to the normal eccentricities of toddlerhood. Even Owen’s teachers expressed surprise when the Johnsons informed his preschool about the formal autism diagnosis, as his outward demeanor still largely mirrored that of his peers.
As time progressed, however, the family watched a heartbreaking transformation occur. Owen shifted from a happy, energetic little boy into a child who was frequently moody and distressed. Within the bustling household he shared with his three sisters—older twins Audrey and Evelyn, alongside his twin sister Alice—Owen still loved music and play. But soon, he began struggling to maintain focus at school, and he eventually stopped participating in the annual Mother’s Day song that he and his siblings had traditionally performed together.
The Johnsons simply could not shake the lingering intuition that Owen’s medical team was missing a critical piece of the puzzle. Yet, in the absence of any medical explanation beyond a standard autism diagnosis, their only recourse was to trust Owen’s pediatrician and therapists, continuously tweaking his behavioral therapies and medications in hopes of finding stability.
"You just want so badly to do something for them and do everything you can to make it better for them," Jennifer Johnson said. "It was very frustrating."
A Suspicious Gene Mutation
While the Johnsons navigated the daily challenges of Owen’s care, Dr. Ryan Dhindsa and his research team across town were deep into an intricate quest to identify genetic risk factors associated with the development of Parkinson’s disease.
Human biology dictates that every child is born with roughly 70 spontaneous genetic mutations that they did not inherit from either parent. The vast majority of these spontaneous DNA alterations are entirely harmless, but a microscopic fraction can disrupt vital biological processes and lead to severe genetic disorders, explained Dhindsa, who serves as a principal investigator at the Duncan NRI and an assistant professor at the Baylor College of Medicine.
"Sometimes we get unlucky, and that [mutation] hits a really important gene," Dhindsa noted.
Pinpointing pathogenic genes within the human genome is a monumental computational challenge, given that human DNA contains more than 3 billion base pairs. To tackle this, Dhindsa’s laboratory leveraged advanced artificial intelligence and machine learning tools to sequence the DNA of approximately 800,000 patients, comparing the genetic profiles of individuals with Parkinson’s disease against those without it.
The massive data analysis revealed a striking pattern: a significant number of Parkinson’s patients carried a mutation in a specific gene designated as ITSN1. This gene is responsible for producing a crucial protein that facilitates communication between brain cells. Over the subsequent years, Dhindsa’s lab conducted rigorous follow-up testing and determined that individuals carrying an ITSN1 genetic variant face a risk of developing Parkinson’s disease that is roughly ten times higher than average.
As the researchers dug deeper into the function and distribution of the gene, they uncovered another critical clue. ITSN1 variants were also appearing at a notably higher frequency in an entirely different patient demographic: children who had been diagnosed with autism and various other neurodevelopmental disorders.
An Obscure Answer
In the middle of 2022, Jennifer Johnson checked her email and found a message from the commercial laboratory that had performed Owen’s genetic testing a full year prior.
The correspondence explained that the facility had recently become aware of emerging academic research identifying ITSN1 variants as "likely pathogenic." This classification meant there was mounting scientific evidence indicating that the mutation could cause neurodevelopmental disorders closely mirroring autism. However, the letter provided no further context, actionable medical advice, or guidance on what this meant for Owen’s long-term prognosis.
Desperate for clarity, the Johnsons scoured the internet, only to hit a wall of dense medical literature that offered no clear answers regarding Owen’s future. To compound their isolation, Owen’s local doctors and therapists had never even heard of the ITSN1 gene.
"There was a little piece of the puzzle that was maybe filled in, but it just didn’t give a clear enough picture," Jennifer Johnson said.
Determined to pursue expert guidance, the Johnsons brought Owen to Texas Children’s Hospital the following year to consult with pediatric neurologist Dr. Sarah Risen. Dr. Risen performed updated genetic evaluations that formally confirmed the presence of the ITSN1 variant. She also adjusted Owen’s medication regimen, shifting him to prescriptions specifically chosen to better target the physiological impacts associated with the genetic variant.
Then, in early 2025, Dr. Risen shared a remarkable development with Owen’s parents: a scientist at the Duncan NRI was actively studying the very same genetic variant as part of his neurological and Parkinson’s research. Dr. Risen arranged an introduction, connecting the family directly with Dr. Dhindsa.
A Puzzling Diagnosis
Dr. Dhindsa’s laboratory is one of only a handful of research groups worldwide studying the ITSN1 gene, largely because the mutation is extraordinarily rare. Epidemiological estimates suggest that roughly one in every 5,000 people is born with an ITSN1 variant, according to Dhindsa.
Despite ongoing scientific inquiry, the variant has continued to baffle researchers because its clinical presentation is remarkably unpredictable. It remains unclear how, or even if, the mutation will manifest phenotypically in a given individual. In approximately 60 percent of cases where a child inherits the ITSN1 variant from a parent, that parent appears completely healthy and unaffected, Dhindsa noted.
Furthermore, children carrying an ITSN1-related syndrome are almost universally given initial diagnoses of autism and attention deficit hyperactivity disorder (ADHD). Yet, curiously, most adults who carry ITSN1 variants and go on to develop Parkinson’s disease later in life report no personal history of neurodevelopmental disorders during their childhood years.
Such profound biological mysteries are an everyday reality for researchers at the Duncan NRI, an institution dedicated entirely to investigating rare pediatric brain disorders and the specific genes that drive them.
Genes serve as an optimal starting point for understanding both how the human brain fails to function properly during development and why certain neural pathways become uniquely vulnerable to premature degradation later in life, explained Dr. Huda Zoghbi, a renowned neurogeneticist and the founding director of the Duncan NRI. Gaining this fundamental knowledge allows scientists to identify potential strategies for intercepting harmful genetic variants or designing targeted medications and therapies to reverse their effects.
"Once you know that," Zoghbi said, "we can then begin to say, ‘How do you reverse it?’"
Complex Genetic Research
Last year, the Johnsons met with Dr. Dhindsa following the publication of a landmark study on which he served as a co-corresponding author, establishing a definitive link between ITSN1 variants and an elevated risk of Parkinson’s disease. The Johnsons are now among a cohort of roughly 20 families partnering directly with Dhindsa’s laboratory to help medical science better understand ITSN1-related syndrome.
A major component of this collaboration involves a natural history study. Dhindsa’s lab is following individuals with ITSN1 variants over an extended period to document how their symptoms evolve across their lifespans. The clinical spectrum is wide; while some individuals experience relatively mild symptoms such as ADHD or moderate learning disabilities, others face severe neurological complications, including epileptic seizures or dramatic language regression that can cause them to lose the ability to speak as late as their teenage years, Dhindsa explained.
Concurrently, the Duncan NRI is utilizing advanced laboratory techniques to probe the cellular mechanisms of ITSN1 variants.
In a painstaking 18-month process, Dhindsa’s lab took a skin tissue sample from Owen and utilized state-of-the-art gene-editing technology to "reprogram" his somatic cells into induced pluripotent stem cells. The researchers then coaxed these stem cells to differentiate into mature brain cells—cultivating lines both with and without the specific ITSN1 variant to observe the functional differences.
Additionally, the lab is utilizing murine models to study how the genetic variant impacts neural architecture in vivo. Researchers will observe these mice across their lifespans to evaluate how the mutation alters learning, memory, and broader cognitive performance.
"There’s very little understanding of how this gene actually can lead to either autism or Parkinson’s, and critically, why some people can be walking around with the variant and healthy while others can’t," Dhindsa said. "We’re trying to understand all the different components of this puzzle."
Bringing Families on the Journey
While the groundbreaking work underway at the Duncan NRI holds immense promise for the future development of therapies and medications capable of treating rare diseases, Dr. Zoghbi emphasized that the scientific process demands patience.
For many families, the initial relief of discovering a tangible genetic explanation for their child’s developmental hurdles can gradually give way to a sense of exhaustion as they confront the lengthy timelines of clinical research. To combat this emotional toll, Zoghbi stresses the importance of keeping families actively integrated into the scientific process.
"We give them hope, but we also take them along with us on the journey," she said. "They know we’re doing all the steps, one by one, and as fast as we can."
For the Johnsons, the inherent unpredictability surrounding ITSN1-related syndrome remains a source of underlying anxiety. Hearing accounts of older children with the same variant who have experienced profound language loss can be deeply unsettling.
Day-to-day management also presents practical hurdles. Because ITSN1 variants are so rare, there is no standardized clinical playbook, requiring the Johnsons to frequently share new academic discoveries directly with Owen’s local therapists.
Even so, the family maintains an outlook rooted in cautious optimism. Owen and his twin sister Alice recently celebrated their tenth birthday. Owen remains an active child who loves playing tag with his siblings and has recently developed a keen fascination with prehistoric dinosaurs.
Furthermore, a newly adjusted medication regimen has yielded tangible improvements in Owen’s daily mood and concentration span. Following a family relocation to Tomball, Owen is thriving in a supportive school environment that accommodates his specific learning needs by integrating his therapists directly into his classroom throughout the school day.
"They help me with work at school," Owen said. "They help me pay attention."
The Johnsons are also continually encouraged by the scientific breakthroughs unfolding at the Duncan NRI. While Owen will likely require dedicated support systems throughout his life, his parents take comfort in the possibility that ongoing research will yield targeted interventions to halt further neurological regression.
"Of course, we would like for him to be an independent, functioning adult one day," Jennifer Johnson said. "We’re hoping [Dr. Dhindsa’s] work can yield that."
