Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy.
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. We uncovered in three cases without POLR3A mutation recessive mutations in POLR3B, which codes for the second largest subunit of Pol III. Mutations in genes coding for Pol III subunits are a major cause of childhood-onset hypomyelinating leukodystrophies with prominent cerebellar dysfunction, oligodontia, and hypogonadotropic hypogonadism.
Neurogenetics of Motion Laboratory, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
Martine
M
Tétreault
Karine
K
Choquet
Simona
S
Orcesi
Davide
D
Tonduti
Umberto
U
Balottin
Martin
M
Teichmann
Sébastien
S
Fribourg
Raphael
R
Schiffmann
Bernard
B
Brais
Adeline
A
Vanderver
Geneviève
G
Bernard
D000595:Amino Acid Sequence; D001483:Base Sequence; D002531:Cerebellum / Q000473:pathology; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D003337:Corpus Callosum / Q000473:pathology; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics / Q000473:pathology; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense / Q000235:genetics*; D012320:RNA Polymerase III / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D018389:Codon, Nonsense; C468558:POLR3B protein, human; D012320:RNA Polymerase III