New Gene Variant Linked to Brain Development Identified in Bengaluru

A team of medical professionals in Bengaluru, India, has identified an unreported variant of the KDM6B gene in a 10-year-old boy experiencing autism and developmental delays. The child displayed several difficulties, including traits associated with Attention-Deficit/Hyperactivity Disorder (ADHD), behavioural challenges, toe-walking, and delays in speech development. Despite undergoing various therapies over the years with minimal improvement, his parents sought additional evaluations to understand the underlying causes of his condition.

To diagnose the boy, doctors conducted a Whole Exome Sequencing test, which evaluates all significant portions of an individual's DNA to identify genetic changes that may contribute to medical issues. This analysis revealed a new mutation associated with Stolerman neurodevelopmental syndrome, a rare condition linked to abnormalities in the KDM6B gene. Notably, this mutation had not been documented in previous cases, thereby expanding the known genetic factors related to autism spectrum disorders.

Prior to genetic testing, routine examinations, including Magnetic Resonance Imaging (MRI) and metabolic screenings, failed to clarify the child’s difficulties. An electroencephalogram (EEG) indicated unusual brain activity, although no seizures were detected, prompting further investigation through genetic analysis.

The study identified a specific nonsense variant (c.4389G>A; p.Trp1463Ter), which is anticipated to impair the KDM6B protein, a crucial component for normal brain growth. Dr Vykunta Raju KN, a pediatric neurologist at the Bangalore Child Neurology and Rehabilitation Centre, remarked on the significance of genetics in understanding complex developmental issues. "The child had multiple behavioural and developmental issues with no clear cause from routine tests. Genetic sequencing helped identify the underlying reason. A confirmed diagnosis assists us in planning therapies more effectively and provides parents with insights into their child's future development," he explained.

Dr Syeda Zubeda, a medical geneticist and senior genetic counsellor at Strand Life Sciences, highlighted the value of genetic testing in uncovering hidden causes in children presenting overlapping conditions. "Many children exhibit developmental delays, behavioural problems, and autistic traits simultaneously. Genetic testing allows us to pinpoint the exact condition," she stated. She also emphasised the importance of counselling for families, noting, "Families require support in comprehending the implications of the mutation, its prognosis, and potential risks for future children. Counselling is essential."

The identification of this novel KDM6B variant contributes to the increasing body of research regarding genetic mutations associated with neurodevelopmental disorders. The medical professionals involved underscored the necessity of early evaluation and genetic testing for children showing significant or unexplained developmental delays, as it can steer treatment options and help prevent recurrence within families.