Apr 22, 2020 · 4H leukodystrophy is caused by mutations in POLR3A, POL3RB, or POLR1C (Bernard et al., 2011; Saitsu et al., 2011; Tetreault et al., 2011; Thiffault et al., 2015). POLR3A and POLR3B encode the largest and second largest subunits (RPC1 and RPC2, respectively) of RNA polymerase III (Pol III). Together, RPC1 and RPC2 form the catalytic center of Pol III.
Leukodystrophy-associated POLR3A mutations down RNA polymerase III (Pol III) is an essential enzyme responsible for the synthesis of several small noncoding RNAs, a number of which are involved in mRNA translation. Recessive mutations in POLR3A, encoding the largest subunit of Pol III, cause POLR3-related hypomyelinating leukodystrophy (POLR3HLD), characterized by deficient central nervous system myelination.
Dec 01, 2018 · Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. Am J Hum Genet 2011; 89:415 423.
Mutations in RNA Polymerase III genes and defective DNA May 01, 2018 · Bernard G, Chouery E, Putorti ML, Tetreault M, Takanohashi A, Carosso G, et al. Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating
POLR3-related Leukodystrophy - Journal of Clinical Imaging POLR3A and POLR3B genes encode for the two largest subunits of the RNA polymerase III enzyme complex and POLR1C encodes for a smaller but vital subunit of this enzyme complex. [2,9,10] Mutations in these genes impair either the proper assembly of the RNA polymerase III enzyme or else impair its ability to bind to DNA.
Mutations in the POLR3A gene have been found in individuals with ataxia and dental abnormalities. Unlike in Pol III-related leukodystrophy (described above), these individuals do not have reduced myelination in the nervous system. When associated with POLR3A gene mutations, ataxia typically begins in adolescence. Affected individuals may also develop rhythmic shaking (tremor) in the arms or
Phenotypic spectrum of POLR3B mutations:isolated Jan 01, 2017 · POLR3B is the second largest subunit of Pol III and, together with POLR3A, forms the enzyme's catalytic centre.15 Similar to PNPLA6, mutations in these polymerase genes can lead to closely related neurological phenotypes including ataxia, delayed dentition and hypomyelination,16 hypomyelination with cerebellar atrophy and hypoplasia of the
Recessive Mutations in POLR3B Encoding RNA Polymerase III Oct 19, 2015 · The diagnosis of 4H leukodystrophy (hypomyelination, hypogonadotropic hypogonadism, and hypodontia) is based on clinical findings and magnetic resonance imaging (MRI). Recently, mutations of the genes encoding Pol III (RNA polymerase III) subunit A (POLR3A) and subunit B (POL3B) have been identified as the genetic causes of hypomyelination. We describe two Polish
POLR3A and POLR3B encode the two catalytic subunits of RNA Polymerase III (Pol III), which synthesizes numerous small non-coding RNAs. We recently reported that mice homozygous for the Polr3a mutation c.2015G > A (p.Gly672Glu) have no neurological abnormalities and thus do not recapitulate the human POLR3-HLD phenotype.Mutations of POLR3A Encoding a Catalytic Subunit of RNA Sep 09, 2011 · Two missense and one insertion mutations in five individuals with TACH were uncovered in POLR3A, which codes for the largest subunit of RNA polymerase III (Pol III). Because these families were mapped to the same locus as leukodystrophy with oligodontia (LO) and presented clinical and radiological overlap with individuals with hypomyelination, hypodontia and hypogonadotropic hypogonadism (4H)