Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online before print November 12, 2008, doi:10.1212/01.wnl.0000333664.90605.23)
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow CME: Take the course for this article:
 Volume 72, Number 1, January 6, 2009
Right arrow All Versions of this Article:
01.wnl.0000333664.90605.23v1
01.wnl.0000333664.90605.23v2
72/1/20    most recent
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fiskerstrand, T.
Right arrow Articles by Bindoff, L. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fiskerstrand, T.
Right arrow Articles by Bindoff, L. A.
Related Collections
Right arrow Peroxisomes
Right arrow Peripheral neuropathy
Right arrow Retina
Right arrow Audition
Right arrow Genetic linkage
Right arrowRelated Article
NEUROLOGY 2009;72:20-27
© 2009 American Academy of Neurology

A novel Refsum-like disorder that maps to chromosome 20

T. Fiskerstrand, MD, PhD, P. Knappskog, PhD, J. Majewski, PhD, R. J. Wanders, PhD, H. Boman, MD, PhD and L. A. Bindoff, MD, PhD

From the Center for Medical Genetics and Molecular Medicine (T.F., P.K., H.B.) and Department of Neurology (L.A.B.), Haukeland University Hospital, Bergen; Department of Clinical Medicine (P.K., H.B., L.A.B.), University of Bergen, Norway; Department of Human Genetics (J.M.), McGill University and Genome Québec Innovation Centre (J.M.), Montreal, Québec, Canada; and Department of Pediatrics and Clinical Chemistry, Laboratory of Genetic Metabolic Diseases (R.J.W.), Academic Medical Center, University of Amsterdam, The Netherlands.

Address correspondence and reprint requests to Professor Laurence Bindoff, Department of Neurology, Haukeland University Hospital, N-5021 Bergen, Norway laurence.bindoff{at}helse-bergen.no

Objective: Clinical and genetic characterization of a neurologic disorder resembling Refsum disease in a Norwegian consanguineous family.

Methods: The affected individuals comprise a brother and sister and their third cousin. The family comes from a small island community and genealogic studies showed that both sets of parents are descendants of a man born in 1585. Based on the hypothesis that this is an autosomal recessive disease and that the patients were homozygous for the same mutation (identical by descent), we used homozygosity mapping to define the genetic locus of this disorder.

Results: This slowly progressive disorder starts in childhood with signs of peripheral neuropathy (pes cavus, tendoachilles contracture). Hearing loss and cataract become evident in the third decade. Subsequently, patients develop a disorder of gait due to the combination of ataxia and spasticity, and a pigment retinopathy. While the clinical picture is reminiscent of Refsum disease, affected individuals have normal phytanic and pristanic acid levels in plasma, as well as normal enzymatic activity for {alpha}-oxidation. We mapped the disease to a 15.96 Mb region on chromosome 20 (20p11.21-q12), containing approximately 200 genes (maximum lod score = 6.3). Sequencing of 23 candidate genes failed to demonstrate detrimental sequence variants.

Conclusions: Our findings show that the clinical syndromes that include Refsum disease are more heterogeneous than previously recognized. We have chosen to report the clinical features and mapping of this novel disorder in the hope that this will permit identification of other families and thus proper genetic characterization.

Abbreviations: HMSN = hereditary motor and sensory neuropathy; IBD = identical by descent; NARP = neuropathy, ataxia, and retinitis pigmentosa; SCA7 = spinocerebellar ataxia type 7.

Editorial, page 13

e-Pub ahead of print on November 12, 2008, at www.neurology.org.

Supported by Helse Vest (Western Norway Regional Health Authority) (911308 to P.K., T.F., H.B.).

Disclosure: The authors report no disclosures.

Received February 6, 2008. Accepted in final form June 12, 2008.


Related Article

A new disease mimicking Refsum syndrome
Thomas D. Bird
Neurology 2009 72: 13. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 NeurologyHome page
T. D. Bird
A new disease mimicking Refsum syndrome
Neurology, January 6, 2009; 72(1): 13 - 13.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by AAN Enterprises, Inc.