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Tribune News Network
Doha
A STUDY by researchers at Weill Cornell Medicine-Qatar (WCM-Q) has revealed the genetic cause of a neurological disorder and the implications it has for marriage.
The research examined the genetics behind cerebellar ataxia, a congenital malformation of the brain whereby the total volume of the cerebellum a part of the brain that regulates muscle activity at the back of the skull is diminished. This can result in the sufferer having problems walking, poor coordination and a tendency to be a 'late developer' as a child. Cerebellar ataxia can also be associated with poor muscle tone, lack of coordination and learning disabilities.
However, because cerebellar ataxia is often an inherited disease, it could have major implications for the consanguineous marriages that are common in Qatar. When the mutated gene that causes the disorder is expressed in a recessive manner, both parents need to have the same recessive gene for some of their children to be affected. Because genes are inherited, it is much more likely that people within an extended family carry the same genes.
Therefore, a consanguineous marriage within a family who carry the mutated recessive gene is much more likely to lead to cerebellar ataxia in the children of that marriage. The implications of such a marriage should, therefore, be carefully thought about and genetic screening considered.
Collaborating investigators from WCM-Q, Weill Cornell Medicine in New York and Hamad Medical Corporation have now discovered an unusual recessive mutation that leads to cerebellar ataxia. Their results were recently published in the 'Annals of Neurology', an influential journal in the field.
The study, entitled 'Mutation in non-coding RNA, RNU12 causes early-onset cerebellar ataxia', was carried out by a team of doctors and scientists including lead researcher Dr Alice Abdel Aleem, WCM-Q's assistant research professor of neuroscience, and assistant research professor of neurology, along with Dr Elizabeth Ross, the Nathan E Cumming professor of neurology and neuroscience, and chair of the Neuroscience Graduate Programme at WCM in New York; Dr Mahmoud Fawzy Elsaid, senior consultant pediatric neurologist in the Department of Pediatrics at Hamad General Hospital; and Dr Tawfeg Ben-Omran, senior consultant and head of clinical and metabolic genetics at Hamad General Hospital.
Dr Abdel Aleem explained that this particular family study was launched after a young woman visited her clinician with symptoms of cerebellar ataxia. Her brother was also found to have the disorder and the researchers asked if they, and their extended family, would take part in research to examine the genetic cause.
Blood samples were taken from two branches of the family and DNA, RNA and protein was extracted. The data was then analysed by the study research team and the WCM-Q Bioinformatics Core. After looking at the entire genome, a rare variation in the DNA sequence of non-protein coding ribonucleic acid (RNA) called 'RNU12' was found. This 'RNU12' variant was associated with affected family members, following the inheritance pattern expected of a recessive gene.
Laboratory investigations carried out by Dr Nader Chalhoub, a post-doctoral associate at WCM-Q, confirmed that the variant impacts the expression and function of 'RNU12'. This is an exciting finding, since most disease-associated mutations identified to date involve the small fraction of the genome that encodes proteins. The non-coding regions that regulate how the genetic blueprint is read by our cells pose a new frontier of genetic investigation that has been challenging to explore.
Dr Abdel Aleem said:"The study will open a new window for screening for cerebellar ataxia. It also shows geneticists how important it is to conduct research on all parts of the genome both protein-coding and non-coding when looking for causes of disease.
"At the national level, because many families here are consanguineous, family members may have the same genetic defect. Therefore, the implications of marriage in such cases should be considered carefully. Genetic counselors can be very helpful in this regard.
"It is also important to raise community awareness about the pivotal role of families who engage in approved genetic studies. This mutation could not have been identified without the participation of both healthy and affected family members."
However, although the research identified the mutation, it did not identify which of the gene(s) that are regulated by 'RNU12', and so are affected by 'RNU12' mutation, are directly responsible for the cerebellar ataxia. That is the subject of further study by Dr Ross at Weill Cornell's parent campus in New York. In collaboration with Dr Abdel Aleem's laboratory, Dr Ross' group will produce and study experimental animal models that are engineered to carry the same mutation as was found in the study family.
The research was made possible by Qatar National Research Fund's NPRP grant 4-099-3-039, the Qatar Foundation Biomedical research programme and the Teebi Project.
