A team of researchers from Columbia University Medical Center (CUMC) published a study on 21st April online in the American Journal of Human Genetics, identifying a new neurodevelopmental syndrome and the genetic mutation behind it. Researchers led the discovery by finding same gene ‘GNB1’ present in 13 individuals responsible for causing a neurodevelopmental syndrome associated with severe developmental delays, abnormal muscle tone, seizures, and eye complications in the affected people.

The findings were made by performing whole-exome (the portion of the genome that encodes for the production of proteins) sequencing on 5,855 individual patients for identifying ‘excess spontaneous’ or ‘non-inherited’ mutations.

According to the scientists, the discovery has allowed pinning the root cause of the syndrome i.e., mutations in a specific gene and will open doors for creating targeted therapies for individuals with this new, currently unnamed syndrome.

Previously the GNB1 induced mutations have only been found in some cancers, but this is the first time the mutations have been linked to a neurodevelopmental disorder. Scientists seem optimistic about finding reasons behind the mutation which results in damage of this sort. GNB1 protein has been found to encode proteins that carry out different functions in the transmission of many different kinds of signals within cells.

The initial analysis done by the scientists at CUMC involved a hundred patients and after sequencing their DNA, three individuals were found to have mutations in a gene called GNB1.

Slave Petrovski, PhD, former research scientist with the Institute for Genomic Medicine at CUMC and the first author of the study, reported that they reached out to their colleagues at other medical centers to cross check if they found similar mutations in any of the patients after sequencing the DNA. “In all, we reviewed sequencing data on 5,855 individuals and found a total of 13 individuals with GNB1 mutations,” he said.

The fellow researcher and study’s leader David B Goldstein, PhD, the John E Borne Professor of Medical and Surgical Research (in Genetics and Development) and Director of the Institute for Genomic Medicine at CUMC, while predicting the likely outcomes of the study, said, “Now that we’ve determined that a small subset of patients with neurodevelopmental disabilities share the same mutations, we can begin to learn about the prognosis of these individuals, how these mutations lead to this syndrome, and how to develop targeted therapies.”

The findings of the discovery have broadened the scope for studying and preventing mutations at genetic level and can be characterized as an important step toward creating targeted therapies for individuals suffering from this syndrome under consideration, characterized by demonstrating major physical and developmental complications.

The researcher also brought it to the attention that the scientists are not certain about the aspect of signaling that gets affected by the mutations in the GNB1 gene and would like to proceed with available knowledge in order to determine exactly how these mutations are causing the disease conditions, along with finding suitable treatment opportunities, adding, “Moving forward, we hope to determine exactly how these mutations cause disease and then use that information to identify druggable targets—completing the entire precision medicine circle for this condition, from gene discovery to functional biology to the development of targeted therapeutics.”

Dr Goldstein also stated that the technique used for the analysis of the DNA sequences (whole-exome sequencing) is currently not a standard part of the evaluation of patients with neurodevelopmental disorders. He believes that more discoveries on the same lines would help to adopt this genetic approach for diagnosing neurodevelopmental disease as a standard practice for all patients portraying symptoms similar to such disabilities.

The study was supported by the Institute for Genomic Medicine (IGM) as part of the Columbia Precision Medicine Initiative (CPMI) and New York-Presbyterian.

Neurodevelopmental disorders are the ailments in which brain along with other parts of the nervous system are not formed properly, leading to problems in normal growth or development of an individual. The major problems occur in the performance of functions of the central nervous system including activities such as learning ability, recognizing emotion, self-control, memory, and speech and language development etc. These disorders show symptoms either in the early infancy stages or can be life-long.

The Journal of Neurodevelopmental Disorders contains detailed research studies on the pathogenesis i.e., mechanism of progression of various neurodevelopment disorders along with development of new approaches for exploring molecular mechanisms associated with such disorders including Asperger syndrome, stereotypic movement disorder, Down syndrome, Mendelsohnn’s syndrome, schizophrenia, autism, attention deficit hyperactivity disorder, Tourette’s syndrome and motor disorders including developmental coordination disorder etc.