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Orphanet J Rare Dis. 2015 Jun 5;10:69. doi: 10.1186/s13023-015-0279-9.

Large exonic deletions in POLR3B gene cause POLR3-related leukodystrophy.

Author information

1
Departments of Pediatrics, Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Center, 1001 Boulevard Décarie, Montréal, QC, H4A 3J1, Canada. mariana.gutierrez@mail.mcgill.ca.
2
Departments of Pediatrics, Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Center, 1001 Boulevard Décarie, Montréal, QC, H4A 3J1, Canada. isabelle.thiffault@mail.mcgill.ca.
3
Center for Pediatric Genomic Medicine, Children's Mercy Hospitals, 2420 Pershing Rd, suite 421, Kansas City, MO, 64108, USA. isabelle.thiffault@mail.mcgill.ca.
4
Departments of Pediatrics, Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Center, 1001 Boulevard Décarie, Montréal, QC, H4A 3J1, Canada. kether.guerrero@mail.mcgill.ca.
5
Department of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain. gabrielangelmartos@yahoo.es.
6
Department of Pediatrics, Universidad Autónoma de Madrid, CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain. gabrielangelmartos@yahoo.es.
7
Departments of Pediatrics, Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Center, 1001 Boulevard Décarie, Montréal, QC, H4A 3J1, Canada. luan.tran@mail.mcgill.ca.
8
WellSpan Pediatric Neurology, WellSpan Medical Group, York, PA, USA. wbenko@wellspan.org.
9
Department of Child Neurology, VU University Medical Center, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands. ms.vanderknaap@vumc.nl.
10
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands. r.vervenne@vumc.nl.
11
Department of Child Neurology, VU University Medical Center, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands. n.wolf@vumc.nl.
12
Departments of Pediatrics, Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Center, 1001 Boulevard Décarie, Montréal, QC, H4A 3J1, Canada. genevieve.bernard@mcgill.ca.

Abstract

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.

PMID:
26045207
PMCID:
PMC4520020
DOI:
10.1186/s13023-015-0279-9
[Indexed for MEDLINE]
Free PMC Article

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