Researchers identify 30 new genes for mental retardation

Islamabad

Researchers in Pakistan, Netherlands, and the United States have identified 30 new (candidate) genes for Mental Retardation; their findings will have a significant role in improving existing diagnostic procedures and treatment strategies.

The earth-breaking research, which has been published in 'Molecular Psychiatry,' a prestigious international journal, was shared with the media at a press conference organised by the Shaheen Zulfiqar Ali Bhutto Medical University (SZABMU, PIMS) here on Tuesday.

The research has been conducted by SZABMU/CEMB, in collaboration with scientists from Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands, and School of Medicine, University of Maryland, USA.

Dr. S. Riazuddin, Prof. Hans van Bokhoven and Prof. Saima Riazuddin have engaged themselves in collaborative studies designed to elucidate the molecular and genetic basis of MR.

Worldwide, 1-3% of the population is affected by MR; its incidence in Pakistan is higher than world average, supposedly because of high degree of consanguinity in the society. There are about 800 genes known to be able to cause MR, if mutated. Resolving this genetic disorder will require translation of basic research findings to improve clinical tools for diagnosis and treatment.

The researchers have reported the results of exome sequencing in 121 large consanguineous families. In 60 families, they identified a single homozygous DNA variant, 30 affecting reported MR genes and 30 in novel candidate ID genes. Potential pathogenicity of these variants was supported by a variety of convincing studies.

In another eight families, segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for MR. It is further convincingly demonstrated that the novel candidate MR genes formed a network significantly enriched for transcriptional co-expression in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood.

In addition, proteins encoded by 12 novel MR genes directly interact with previously reported MR proteins in six known pathways essential for cognitive function.

"These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of MR. Thus, these findings further expand the existing repertoire of genes involved in MR, and provide new insights into the molecular mechanisms and the transcriptome map of MR," the media was told.

These findings, together with results, which are expected to be released during the next 8-10 months, will have a significant role in improving the existing diagnostic procedures as well as treatment strategies.