title: Large exonic deletions in POLR3B gene cause POLR3-related leukodystrophy.
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.
authors.affiliation: 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.
authors.forename: Mariana
authors.initials: M
authors.lastname: Gutierrez
authors.affiliation: 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.|Center for Pediatric Genomic Medicine, Children's Mercy Hospitals, 2420 Pershing Rd, suite 421, Kansas City, MO, 64108, USA. isabelle.thiffault@mail.mcgill.ca.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thiffault
authors.affiliation: 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.
authors.forename: Kether
authors.initials: K
authors.lastname: Guerrero
authors.affiliation: Department of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain. gabrielangelmartos@yahoo.es.|Department of Pediatrics, Universidad Autónoma de Madrid, CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain. gabrielangelmartos@yahoo.es.
authors.forename: Gabriel Á
authors.initials: GÁ
authors.lastname: Martos-Moreno
authors.affiliation: 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.
authors.forename: Luan T
authors.initials: LT
authors.lastname: Tran
authors.affiliation: WellSpan Pediatric Neurology, WellSpan Medical Group, York, PA, USA. wbenko@wellspan.org.
authors.forename: William
authors.initials: W
authors.lastname: Benko
authors.affiliation: Department of Child Neurology, VU University Medical Center, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands. ms.vanderknaap@vumc.nl.
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands. r.vervenne@vumc.nl.
authors.forename: Rosalina M L
authors.initials: RM
authors.lastname: van Spaendonk
authors.affiliation: Department of Child Neurology, VU University Medical Center, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands. n.wolf@vumc.nl.
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
authors.affiliation: 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.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bernard
mesh_terms: D000293:Adolescent; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D012320:RNA Polymerase III / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: C468558:POLR3B protein, human; D012320:RNA Polymerase III