Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies with or without dental abnormalities and/or hypogonadotropic hypogonadism

Leukodystrophies are a group of hereditary neurodegenerative disorders characterized by abnormal white matter on brain imaging. Hypomyelinating leukodystrophies are a subtype of leukodystrophies caused by abnormal myelin deposition. Recently, our group reported that mutations in POLR3A and POLR3B genes were responsible for four hypomyelinating leukodystrophies with or without dental abnormalities and delayed puberty, and are now referred as Pol III-related leukodystrophies. The objective of this study was to determine the frequency of POLR3A and POLR3B mutations in patients with typical clinical and/or radiologic features of Pol III-related leukodystrophies. To do so, we sequenced the POLR3A and/or POLR3B genes in fourteen patients and found mutations in all fourteen patients, including eight novel mutations in POLR3A and seven novel mutations in POLR3B. To date, our group has described 37 patients, of whom 27 have mutations in POLR3A and 10 in POLR3B, respectively. Altogether, our results further support that POLR3A and POLR3B mutations are a major cause of hypomyelinating leukodystrophies and suggest that POLR3A mutations are more frequent. (By Dr. Geneviève Bernard, http://jmg.bmj.com/content/early/2013/01/24/jmedgenet-2012-101357 )

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