Large exonic deletions in POLR3B gene cause POLR3-related leukodystrophy.
POLR3-related (or 4H) leukodystrophy is an autosomal recessive disorder caused by mutations in POLR3A or POLR3B and is characterized by neurological and non-neurological features. In a small proportion of patients, no mutation in either gene or only one mutation is found. Analysis of the POLR3B cDNA revealed a large deletion of exons 21-22 in one case and of exons 26-27 in another case. These are the first reports of long deletions causing POLR3-related leukodystrophy, suggesting that deletions and duplications in POLR3A or POLR3B should be investigated in patients with a compatible phenotype, especially if one pathogenic variant has been identified.
Orphanet J Rare Dis
Adolescent; Exons; Female; Genes, Recessive; Hereditary Central Nervous System Demyelinating Diseases; Humans; Infant; Male; RNA Polymerase III; Sequence Deletion
Exons; Genes, Recessive; Hereditary Central Nervous System Demyelinating Diseases; RNA Polymerase III; Sequence Deletion
Gutierrez, M., Thiffault, I., Guerrero, K., Martos-Moreno, G. A., Tran, L., Benko, W., van der Knaap, M. S., van Spaendonk, R. M., Wolf, N. I., Bernard, G. Large exonic deletions in POLR3B gene cause POLR3-related leukodystrophy. Orphanet J Rare Dis 10, 69-69 (2015).