Breaking News – Mystery Gene found for brain disease by Indian Researchers,Genetists from Sir Ganga Ram Hospital and Maulana Azad Medical College help global researchers identify cause for inherited brain disorder.

Mystery Gene found for brain disease by Indian Researchers

 Genetists from Sir Ganga Ram Hospital and Maulana Azad Medical College help global researchers identify cause for inherited brain disorder

Identified for the first time that Mutation (changes) in DARS gene cause HBSL (Hypomyelination with Brain Stem and Spinal Cord Involvement and Leg Spasticity)

A global team of researchers has identified causative gene behind the disease of  4 year old Indian child with a  brain disorder along with nine other children around the globe ,  in a discovery that is paving the way for the diagnosis and treatment of other children with genetic diseases. It has been found that mutations in DARS  gene  is responsible for causing inherited brain disorder called HBSL (Hypomyelination with Brain Stem and Spinal Cord Involvement and Leg Spasticity).

The team, consisting of sixteen researchers including Dr I.C.Verma , Director , Centre for Medical Genetics , Sir Ganga Ram Hospital and Dr Monica Juneja , Department of Pediatrics , Maulana Azad Nedical Colleger led by Dr Ryan Taft from The University of Queensland’s, used genome sequencing to determine that these children were  suffering from a defect in a gene  previously not associated with human disease.

“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 his disorder,” Dr Taft said.

“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.”

“This gene has never previously been associated with human disease and may not have been identified as the culprit using any other method,” said Dr I.C.Verma , Head of Genetics at Sir Ganga Ram Hospital.

This 4 year old child from Punjab was suffering from motor developmental delay . He could not walk and sit  without support .

The team, comprising of experts from Sir Ganga Ram Hospital and Maulana Azad Medical College , Delhi , India and IMB in Brisbane, VU University Medical Center in Amsterdam, Murdoch Children’s Research Institute and The Royal Children’s Hospital in Melbourne, and Children’s National Medical Center in Washington D.C., has published their findings in the American Journal of Human Genetics in volume -92  May 2013 edition. (attached).

In this path breaking research Dr I.C. Verma was assisted by his team of researchers at SGRH consisting of Dr Udhaya Kotecha , Dr Ratna Puri , Dr Sunita Bijarnia and Dr Jyotsana Verma.

Dr 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.”

“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,” added Dr Verma.

“Our goal is to dramatically reduce the number of unresolved pediatric cases of rare genetic disease,” Dr Taft said.

The technology of exome sequencing and whole sequencing now allows doctors to find the cause of disease in many children with unknown brain disorders . We have used exome based targetted next generation sequencing to identify the culprit gene in other patients also.

At present 30-40 % of patients with intellectual disability go undiagnosed in India . The new techniques will remarkably reduce this number. Discovering the causative gene will help in providing genetic counseling to the family . It will also ensure that they have normal children .

 Dr I.C.Verma reflects in Indian Journal of Pediatrics journal , 2001 , in Burden of Genetic Disorders in India , “India, like other developing countries, is facing an accelerating demographic switch to non-communicable diseases. In the cities congenital malformations and genetic disorders are important causes of morbidity and mortality. Due to the high birth rate in India a very large number of infants with genetic disorders are born every year almost half a million with malformations and 21,000 with Down syndrome. In a multi-centric study on the causes of referral for genetic counselling the top four disorders were repeated abortions (12.4%), identifiable syndromes (12.1%), chromosomal disorders (11.3%) and mental retardation (11%). In a more recent study in a private hospital the top reasons for referral were reproductive genetics (38.9%)–comprising prenatal diagnosis, recurrent abortions, infertility and Torch infections–mental retardation +/- multiple congenital anomalies (16.1%), Down syndrome (9.1%), thalassemia/haemophilia (8.8%), and muscle dystrophy/spinal muscular atrophy (8.4%). The disorders for which prenatal has been done over an 18-month-period are given. A recent study carried out in three centers (Mumbai, Delhi and Baroda) on 94,610 newborns by using a uniform proforma showed a malformation frequency of 2.03%, the commonest malformations are neural tube defects and musculo-skeletal disorders. The frequency of Down syndrome among 94,610 births was 0.87 per 1000, or 1 per 1150. Screening of 112,269 newborns for aminoacid disorders showed four disorders to be the commonest–tyrosinemia, maple syrup urine disease and phenylketonuria. Screening of cases of mental retardation for aminoacid disorders revealed four to be the commonest–hyperglycinemia, homocystinuria, alkaptonuria, and maple syrup urine disease. Metabolic studies of cases of mental retardation in AIIMS, Delhi and KEM Hospital, Mumbai, demonstrated that common disorders were those of mucopolysaccharides, lysosomes, Wilson disease, glycogen storage disease and galactosemia. It is estimated that beta- thalassemia has a frequency at birth of 1:2700, which means that about 9,000

cases of thalassemia major are born every year. Almost 5200 infants with sickle cell disease are born every year. Disorders, which deserve to be screened in the newborn period, are hypothyroidism and G-6-PD deficiency, while screening for aminoacid and other metabolic disorders could presently be restricted to symptomatic infants.”