New Delhi: In a
discovery that is paving the way for the diagnosis and treatment
of a rare genetic disorder related to the brain's functioning, a
team of researchers has identified the causative gene behind the
disease, which delays development of motor activities in children.
The study was done on a four-year-old child from Punjab, and nine
other children who were suffering from motor developmental delay.
They could not walk and sit without support.
The team, led by Ryan Taft of the University of Queensland's
Institute for Molecular Bioscience (IMB), comprised 16 researchers
including I.C. Verma, director, Centre for Medical Genetics, Sir
Ganga Ram Hospital and Monica Juneja, Department of Paediatrics,
Maulana Azad Medical College.
The doctors used genome sequencing to determine that these
children were suffering from a defect in a gene previously not
associated with human disease.
"It has been found that mutations in a gene called DARS gene is
responsible for causing inherited brain disorder called HBSL (Hypomyelination
with Brain Stem and Spinal Cord Involvement and Leg Spasticity),
which affects the motor development activities," a statement from
the doctors said.
"We analysed the genome sequences of this child and his parents,
using a method called whole genome sequencing and found that a
mutation in the DARS gene was likely causing the disorder," Taft
"In collaboration with clinicians from India, Canada, Netherlands,
Australia, and the US, we then examined the genomes of nine other
children who appeared to be suffering from the same disease and
the genomes of their parents, and confirmed that they all had
mutations in the DARS gene," he said.
"This gene has never previously been associated with human disease
and may not have been identified as the culprit using any other
method," said Verma, who heads the department of genetics at Sir
Ganga Ram Hospital.
Experts from Sir Ganga Ram Hospital and Maulana Azad Medical
College, Delhi, India and IMB in Brisbane, Vrije Universiteit
Medical Center in Amsterdam, Murdoch Children's Research Institute
and The Royal Children's Hospital in Melbourne, and Children's
National Medical Centre in Washington D.C came together for this
Verma elaborated: "They have named the disease HBSL because it
causes Hypomyelination in the brain stem and spinal cord, leading
to leg spasticity. Hypomyelination occurs when people do not have
enough myelin, the substance that coats nerve fibres and enables
the transmission of electrical impulses in the nervous system."
"Our goal is to dramatically reduce the number of unresolved
paediatric cases of the rare genetic disease," said Taft.
The technology of exome sequencing and whole sequencing now allows
doctors to find the cause of disease in many children with unknown
brain disorders. The doctors say they have used exome-based
targetted next generation sequencing to identify the culprit gene
in other patients also.
At present 30 to 40 percent of patients with intellectual
disability go undiagnosed in India. Doctors say the new techniques
will remarkably reduce this number.
"Discovering the causative gene will help in providing genetic
counselling to the family. It will also ensure that they have
normal children," Verma said.
"This is the future of medicine - doctors, including clinical
specialists like MRI experts - and genomics researchers working
together to diagnose and develop treatments for people with
unknown diseases," he added.