Some people have an immense urge to sleep at inappropriate times and places. This rare disorder is referred to as Narcolepsy and a vast majority of cases are believed to be an outcome of complex mechanisms, except for a small percentage of cases that are linked with unidentified inherited mutations. “Cataplexy,” or a sudden muscle weakness elicited by strong emotions, is a unique characteristic seen in Narcoleptics. In a new study published in the American Journal of Human Genetics, researchers discover that a certain genetic mutation triggered narcolepsy in a large family affected by the disorder. The research provides intriguing insights into the genetics of inherited narcolepsy and sheds new light on complex neuropsychiatric disorders.
Senior study author, Dr. Rosa Peraita-Adrados from the Gregorio Marañón University Hospital in Madrid, Spain, said: “The cause of this rare form of inherited narcolepsy has been very difficult to study and is not well understood. To identify a causative mutation in familial narcolepsy, we performed a genetic analysis in the largest-ever reported family with twelve affected members and then performed an even more sensitive analysis of three affected members with narcolepsy and cataplexy.”
The research team involving Dr. Peraita-Adrados, co-author Dr. Mehdi Tafti from the University of Lausanne in Switzerland, and their colleagues found that the affected family members harbored a mutation in the myelin oligodendrocyte gene (MOG), which was absent in unaffected family members or unrelated controls.
The oligodendrocytes, or the support cells in the central nervous system, produce a protein called Myelin that is vital for the proper functioning of the nervous system. Researchers found an inappropriate distribution of MOG protein within the cells after inserting an abnormal MOG into mouse oligodendrocytes, which suggested the possible non-functionality of mutant MOG.
Advance research is required to confirm the association between myelin, oligodendrocytes, and narcolepsy. However, the finding is fascinating, in particular, because in recent times MOG has been associated with various neuropsychiatric disorders.
To conclude, Sr. Tafti said, “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. 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.”