Rare brain disorder identified, explained thanks to genomic research

Research to identify an Australian boy's mystery illness, which ultimately involved scientists around the world, has led to the identification of a new paediatric brain disorder, as well as the faulty gene behind the condition.

The boy, Massimo Damiani, had a 'sudden developmental regression' shortly after his first birthday, his father, Stephen, says.

'Initially, all doctors could tell us was that he was suffering from a leukodystrophy, a group of diseases that cause developmental delays and often premature death, which 50 percent [of the time] remain undiagnosed'.

However, Dr Ryan Taft of The University of Queensland, Australia, used whole genome sequencing to analyse Massimo's and his parents' genetic code and pinpoint the malfunctioning gene.

The gene in question — DARS, aspartyl-tRNA synthetase [cytoplasmic] — had 'never previously been associated with human disease and may not have been identified as the culprit using any other method', Dr Taft explained.

The team then reached out to clinicians and researchers around the world to see if other children, also diagnosed with an unknown leukodystrophy or similar, might actually have the same illness as Massimo. Genetic analysis of nine other children revealed mutations in DARS.

The researchers have named the disease HBSL as a loose acronym for 'Hypomyelination in the brain stem and spinal cord leading to leg spasticity'. Hypomyelination refers to a lack of myelin - the material coating nerve fibres which enables the transmission of nervous impulses.

Children with HBSL cannot sit or walk without support due to delayed development of the nervous system. This lack of mobility increases their risk of developing serious infections. The mechanism through which DARS causes the disorder remains unclear.

Dr Taft's team hope the methods used in this study will enable similar Genetic condition to be identified. The group has already identified the gene responsible for H-ABC (hypomyelination with atrophy of the basal ganglia and cerebellum), another leukodystrophy.

Dr Taft says: 'This is the future of medicine - doctors, including clinical specialists like MRI experts, and genomic researchers working together to diagnose and develop treatments for people with unknown diseases'.

The study was published in The American Journal of Human Genetics and involved researchers from Australia, Canada, the Netherlands, the USA and India.