POLR3A and POLR3B Mutations in Unclassified Hypomyelination

Ferdy K. Cayami; Roberta La Piana; Rosalina M. L. van Spaendonk; Miriam Nickel; Annette Bley; Kether Guerrero; Luan T. Tran; Marjo S. van der Knaap; Geneviève Bernard; Nicole I. Wolf

doi:10.1055/s-0035-1550148

Neuropediatrics, Inhaltsverzeichnis

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^*

¹Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands

²Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands

,

Roberta La Piana^*

³Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada

,

Rosalina M. L. van Spaendonk

²Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands

,

Miriam Nickel

⁴Department of Pediatrics, Clinic for Degenerative Brain Disorders, University Medical Center Hamburg Eppendorf, Hamburg, Germany

,

Annette Bley

⁴Department of Pediatrics, Clinic for Degenerative Brain Disorders, University Medical Center Hamburg Eppendorf, Hamburg, Germany

,

Kether Guerrero

³Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada

,

Luan T. Tran

³Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada

,

Marjo S. van der Knaap

¹Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands

,

Geneviève Bernard^‡

³Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada

,

Nicole I. Wolf^‡

¹Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands

› Institutsangaben

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.

Keywords

hypomyelination - MRI - 4H syndrome - POLR3A - POLR3B

Volltext

Referenzen

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