title: POLR3A and POLR3B Mutations in Unclassified Hypomyelination.
abstract: OBJECTIVE
  This study aims to ascertain frequency of mutations in POLR3A or POLR3B, which are associated with 4H leukodystrophy, in a cohort of patients with unclassified hypomyelination.
  
  
  RESULTS
  In a cohort of 22 patients with the magnetic resonance imaging (MRI) diagnosis of unclassified hypomyelination and without typical clinical signs, we evaluated clinical and MRI features. Developmental delay or intellectual disability, ataxia, and spasticity were frequent symptoms. POLR3A and POLR3B were sequenced. A compound heterozygote mutation in POLR3B was found in only one patient. Additional investigations allowed a definitive diagnosis in 10 patients.
  
  
  CONCLUSIONS
  Mutations in POLR3A or POLR3B are rare in patients with unclassified hypomyelination, and alternative diagnoses should be considered first.
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ferdy K
authors.initials: FK
authors.lastname: Cayami
authors.affiliation: Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada.
authors.forename: Roberta
authors.initials: R
authors.lastname: La Piana
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Rosalina M L
authors.initials: RM
authors.lastname: van Spaendonk
authors.affiliation: Department of Pediatrics, Clinic for Degenerative Brain Disorders, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Nickel
authors.affiliation: Department of Pediatrics, Clinic for Degenerative Brain Disorders, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Bley
authors.affiliation: Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada.
authors.forename: Kether
authors.initials: K
authors.lastname: Guerrero
authors.affiliation: Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada.
authors.forename: Luan T
authors.initials: LT
authors.lastname: Tran
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
authors.affiliation: Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bernard
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003711:Demyelinating Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D002658:Developmental Disabilities / Q000209:etiology / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D012320:RNA Polymerase III / Q000235:genetics*; D055815:Young Adult
chemical_list: C585825:POLR3A protein, human; C468558:POLR3B protein, human; D012320:RNA Polymerase III