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5 new gene mutations found, making a significant contribution to an international database.

A collaborative study conducted by researchers at the Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science (IISc) and the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, has analyzed DNA samples of Indian families to study brain diseases. Headed by Dr. Arun Kumar from IISc and Dr. P. S. Bindu from NIMHANS, it is the first report on the genetic analysis of 22 Indian families with neurodegenerative diseases caused by alterations in a specific gene called PLA26G.

This gene provides instruction in making an enzyme that helps in breaking down fats called phospholipids in our body. Alterations in this gene cause neurological disorders, which lead to slower body movements, tremors and problems with vision and brain function. These symptoms appear in the first 2 years of life, causing death by 10 years. There are three types of conditions caused by mutations in this gene and one of them is commonly known as Seitelberger’s disease (Classic Infantile Neuroaxonal Dystrophy). In some cases, the symptoms appear later in the childhood and progress slowly and are found in a condition called ANAD (Atypical Late-onset Neuroaxonal Dystrophy). The third condition is called DPC (Dystonia Parkinsonism Complex). There has been extensive research done around the world to find out what goes wrong in the DNA of a person who is suffering from these diseases. However, this is the first time that Indian patients have been examined for these conditions.

The researchers analyzed a total of 22 Indian individuals suffering from these diseases and their parents and siblings. Blood samples were collected and DNA was extracted from the samples. The isolated DNA was then multiplied into several copies to further identify the abnormalities in the DNA. “This whole process could take about two weeks after the blood sample is collected”, says Prof. Arun Kumar. The DNA from all 22 families was scrutinized to identify a unique type of mutation, which is the primary cause of the disease.

A thorough examination of all the families revealed 5 new unique mutations that have never been found until now. These mutations were found only in12 families out of a total number of 22 families. There were no mutations found in the rest of the 10 families. These 5 new mutations add to the 124 mutations already identified across the world. Now the total number of mutations identified stands at 129.The reason for the absence of mutation in the rest of the 10 families could be that the mutation is in a deep intronic region of the gene and could not be detected by the process used for this study.

The same type of mutation can be found in more than one individual/family in different parts of the world. This means that it is quite possible that an American suffering from this disease may have the same mutation as an Indian. And hence, these results from the study play an important role in understanding the cause of the disease worldwide.This information can be used for genetic counseling to prevent the occurrence of the disease in the new generation. Even a person who is not suffering from the disease can be a carrier. And if 2 individuals, who are carriers get married, there is a possibility that their children might suffer from the disease. “To avoid this situation, the data of this study has been given to clinicians, who have in turn informed the families in case they wish to find out about the carrier status of any individual. Our lab can help them with the further analysis”, confirms Prof. Arun Kumar.

This research has made a significant contribution to the international database of the mutations of gene PLA26G and the present findings will not only be useful families that were examined, but also to those with similar neurodegenerative conditions living across the world.


About the authors

Arun Kumar is a Professor at the Department of Molecular Reproduction, Development and Genetics, IISc.

Dr. P.S.Bindu is a Neurologist at the National Institute of Mental Health and Neurosciences, Bangalore.

About the paper

The paper was published on May 19, 2016 in the journal PLoS ONE.