Researchers link mutation with inherited narcolepsy
A European team of researchers has identified the mutation that triggers narcolepsy in a large family impacted by this rare disorder. Published in the American Journal of Human Genetics, the findings provide new insight on the genetics of inherited narcolepsy as well as other complex neuropsychiatric diseases.
Narcolepsy is a rare condition characterised by frequent and uncontrollable urges to sleep at inappropriate times and places. Researchers say people suffering from this disorder may also deal with 'cataplexy', a sudden muscle weakness that is brought on by strong emotions. While most narcolepsy cases are believed to be brought on by complex mechanisms, some cases are linked to inherited mutations that have yet to be identified.
In this latest study, the researchers from Spain and Switzerland performed a genetic analysis in the largest-reported family suffering from this disease.
'The cause of this rare form of inherited narcolepsy has been very difficult to study and is not well understood,' says Dr Rosa Peraita-Adrados from the Gregorio Marañón University Hospital in Madrid, Spain. 'To identify a causative mutation in familial narcolepsy, we performed a genetic analysis in the largest-ever reported family with 12 affected members and then performed an even more sensitive analysis of 3 affected members with narcolepsy and cataplexy.'
Dr Peraita-Adrados, working together with Dr Mehdi Tafti of the University of Lausanne in Switzerland and colleagues, discovered that the myelin oligodendrocyte gene (MOG) in the family members impacted by this disease had a mutation not found in unaffected family members or in hundreds of unrelated controls.
Oligodendrocytes, which provide support to cells in the central nervous system, produce the myelin protein, a key material in the myelin sheath that ensures the proper functioning of the nervous system. The team discovered that the MOG protein was not properly distributed within the cells, leading them to consider that the mutant MOG fails to work properly.
The team notes that while more research is required to identify the links between myeline, oligodendrocytes and narcolepsy, the results provide key information particularly since MOG was recently linked to other neuropsychiatric illnesses.
'Gene-expression studies in major depression, bipolar disorder, schizophrenia, and multiple sclerosis indicate that genes expressed in oligodendrocytes are downregulated, supporting the hypothesis that problems with oligodendrocytes might cause neurodevelopmental disorders,' Dr Tafti says. 'The identification of a mutation in MOG, so far unique to our family, not only provides insight into the pathogenesis of narcolepsy but also highlights the role of myelin and oligodendrocytes in disease susceptibility in other complex neuropsychiatric disorders.'