congenital hypomyelinating diseases
Monday 14 November 2011
Congenital hypomyelinating diseases are a heterogeneous group of inherited leukoencephalopathies characterized by abnormal myelin formation.
Mutations in POLR3A encoding the largest subunit of RNA polymerase III (Pol III) were found to be responsible for the majority of cases presenting with three clinically overlapping hypomyelinating leukodystrophy phenotypes.
POLR3B codes for the second largest subunit of Pol III.
Mutations in genes coding for Pol III subunits (POL3s) are a major cause of childhood-onset hypomyelinating leukodystrophies with prominent cerebellar dysfunction, oligodontia, and hypogonadotropic hypogonadism.
Perturbation of Pol III target transcription, especially of tRNAs, could be a common pathological mechanism underlying POLR3A and POLR3B mutations.
Recessive Mutations in POLR3B, Encoding the Second Largest Subunit of Pol III, Cause a Rare Hypomyelinating Leukodystrophy. Tétreault M, Choquet K, Orcesi S, Tonduti D, Balottin U, Teichmann M, Fribourg S, Schiffmann R, Brais B, Vanderver A, Bernard G. Am J Hum Genet. 2011 Oct 26. PMID: 22036172
Mutations in POLR3A and POLR3B Encoding RNA Polymerase III Subunits Cause an Autosomal-Recessive Hypomyelinating Leukoencephalopathy. Saitsu H, Osaka H, Sasaki M, Takanashi JI, Hamada K, Yamashita A, Shibayama H, Shiina M, Kondo Y, Nishiyama K, Tsurusaki Y, Miyake N, Doi H, Ogata K, Inoue K, Matsumoto N. Am J Hum Genet. 2011 Oct 25. PMID: 22036171