09 July 2020
Genes linked to intellectual disability
Published online 1 October 2011
Most research into early-onset cognitive impairment has focused on X-chromosome-linked intellectual disability (XLID), a form of mental retardation associated with the X-chromosome and which is more common in males. Researchers have already implicated over 90 different gene mutations in XLID, but it accounts for less than 10% of intellectual disability cases, which means the vast majority of genetic defects may be autosomal.
In a bid to search for these lesser known genetic defects, researchers from Iran, Germany, Canada and geneticist Anna Rajab at Royal Hospital in Muscat,Oman performed next-generation sequencing on members of 136 consanguineous families with autosomal-recessive intellectual disability. The preponderance of large consanguineous families in North Africa and the Middle East makes the region fertile ground to study the role of autosomal recessive intellectual disability (ARID), explain the researchers.
The study managed to identify 76 mutations to individual genes within 78 of the families studied that the researchers suggest could be disease-causing. Fifty of these gene varients were novel and not linked to ARID. There are almost no common forms of ARID. Only two of these mutations appeared in two different families, which adds further proof to the researchers' claim that ARID is very heterogeneous in nature.
Several of the mutations included small or whole-exon deletions, gene frameshifts and nonsense mutations as well as incomplete proteins. Very few of the mutated genes were specific to neurons, with the majority of these proteins involved in crucial cellular processes, such as energy metabolism, transcription and translation, which are pivotal for normal brain function and development. It is still unclear why the effects are confined to the brain, even though these proteins function throughout the body.
These findings may open up new ways to diagnose and prevent certain forms of intellectual disability, and even treat some forms of ARID. Moreover, the researcher team speculate that this study may be a model for the elucidation of other common diseases which, like ARID, may be caused by many different gene defects.
- Najmabadi, H. et al. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature (21 September 2011) doi: 10.1038/nature10423