Myelin Dysfunction in MS and Other White Matter Diseases Found to Be Linked to Specific Gene Mutations

In a new study, researchers have revealed the previously unknown function of the FAM126A gene in supporting myelination (the formation of the myelin sheath that protects neurons), a critically important process in the development and recovery of acute exacerbations in multiple sclerosis (MS). The research paper, entitled “The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane,” was recently published in the journal Nature Cell Biology.

Mutations in the gene FAM126A, whose corresponding protein is also called hyccin, have been reported to cause a number of medical conditions, namely developmental and intellectual delays, peripheral neuropathy, muscle wasting, and hypomyelination and congenital cataract (HCC). This last condition is categorized as a leukodystrophy, a poorly understood group of white matter diseases caused by genetic defects in the formation and maintenance of myelin.

Though mutations in FAM126A are known to contribute to these series of pathologies, the exact role of the gene is unknown. Now, according to a Yale news release, researchers from the Yale University School of Medicine in collaboration with other research institutes from the U.S., Italy and Germany have shown that FAM126A regulates the synthesis of phosphatidylinositol 4-phosphate PtdIns(4)P, an important bioprecursor of a plasma membrane phospholipid crucial to the myelination process, allowing the protection of neurons across the nervous system and the quick movement of nerve impulses between brain cells.

Through the analysis of fibroblast cells of patients suffering from HCC, researchers were able to conclude that FAM126A mutations destabilize an enzyme complex essential to the production of myelin. The scientists propose that HCC pathogenesis involves defects on the production of [PtdIns(4)P] in oligodendrocytes, cells that produce myelin in the central nervous system.

MS development is deeply related to the damage of the protective myelin sheath by the body’s own immune cells, which can ultimately result in neuron damage and death. The research presented by Yale scientists is key to the study of MS pathogenesis and the development of possible new therapeutic targets for the disease, especially since the FAM126A protein was found to play a crucial role in the normal myelination of the central nervous system and possibly in the recovery of MS patients.