Neuropediatrics 2015; 46(03): 221-228
DOI: 10.1055/s-0035-1550148
Original Article
Georg Thieme Verlag KG Stuttgart · New York

POLR3A and POLR3B Mutations in Unclassified Hypomyelination

Ferdy K. Cayami*
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
2   Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
,
Roberta La Piana*
3   Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada
,
Rosalina M. L. van Spaendonk
2   Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
,
Miriam Nickel
4   Department of Pediatrics, Clinic for Degenerative Brain Disorders, University Medical Center Hamburg Eppendorf, Hamburg, Germany
,
Annette Bley
4   Department of Pediatrics, Clinic for Degenerative Brain Disorders, University Medical Center Hamburg Eppendorf, Hamburg, Germany
,
Kether Guerrero
3   Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada
,
Luan T. Tran
3   Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada
,
Marjo S. van der Knaap
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
,
Geneviève Bernard
3   Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada
,
Nicole I. Wolf
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

24 November 2014

13 February 2015

Publication Date:
08 May 2015 (online)

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.

Methods and 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.

Conclusion Mutations in POLR3A or POLR3B are rare in patients with unclassified hypomyelination, and alternative diagnoses should be considered first.

* These authors contributed equally to this work.