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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism
Brain, Volume 133, No. 11, Year 2010
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Description
Cerebellar hypoplasia and slowly progressive ophthalmological symptoms are common features in patients with congenital disorders of glycosylation type I. In a group of patients with congenital disorders of glycosylation type I with unknown aetiology, we have previously described a distinct phenotype with severe, early visual impairment and variable eye malformations, including optic nerve hypoplasia, retinal coloboma, congenital cataract and glaucoma. Some of the symptoms overlapped with the phenotype in other congenital disorders of glycosylation type I subtypes, such as vermis hypoplasia, anaemia, ichtyosiform dermatitis, liver dysfunction and coagulation abnormalities. We recently identified pathogenic mutations in the SRD5A3 gene, encoding steroid 5α-reductase type 3, in a group of patients who presented with this particular phenotype and a common metabolic pattern. Here, we report on the clinical, genetic and metabolic features of 12 patients from nine families with cerebellar ataxia and congenital eye malformations diagnosed with SRD5A3-congenital disorders of glycosylation due to steroid 5α-reductase type 3 defect. This enzyme is necessary for the reduction of polyprenol to dolichol, the lipid anchor for N-glycosylation in the endoplasmic reticulum. Dolichol synthesis is an essential metabolic step in protein glycosylation. The current defect leads to a severely abnormal glycosylation state already in the early phase of the N-glycan biosynthesis pathway in the endoplasmic reticulum. We detected high expression of SRD5A3 in foetal brain tissue, especially in the cerebellum, consistent with the finding of the congenital cerebellar malformations. Based on the overlapping clinical, biochemical and genetic data in this large group of patients with congenital disorders of glycosylation, we define a novel syndrome of cerebellar ataxia associated with congenital eye malformations due to a defect in dolichol metabolism. © 2010 The Author.
Authors & Co-Authors
Morava, Éva
Netherlands, Nijmegen
Radboud University Medical Center
Wevers, Ron Allan
Netherlands, Nijmegen
Radboud University Medical Center
Cantagrel, Vincent
United States, La Jolla
Department of Neurosciences
Hoefsloot, Lies H.
Netherlands, Nijmegen
Radboud University Medical Center
Al-Gazali, Lihadh I.
United Arab Emirates, Al Ain
United Arab Emirates University
Schoots, Jeroen
Netherlands, Nijmegen
Radboud University Medical Center
Van Rooij, Arno
Netherlands, Nijmegen
Radboud University Medical Center
Huijben, Karin M.L.C.
Netherlands, Nijmegen
Radboud University Medical Center
Van Ravenswaaij-Arts, Conny M.A.
Netherlands, Groningen
Rijksuniversiteit Groningen
Jongmans, Marjolijn C.
Netherlands, Nijmegen
Radboud University Medical Center
Sykut-Cegielska, Jolanta
Poland, Warsaw
Instytut Pomnik - Centrum Zdrowia Dziecka
Hoffmann, Georg Friedrich
Germany, Heidelberg
Universitätsklinikum Heidelberg
Bluemel, Peter
Austria, Vienna
Gottfried V Preyer Kinderspital
Adamowicz, Maciej
Unknown Affiliation
van Reeuwijk, Jeroen V.
Netherlands, Nijmegen
Radboud University Medical Center
Ng, Bobby George
United States, San Diego
Sanford Burnham Prebys Medical Discovery Institute
Bergman, Jorieke E.H.
Netherlands, Groningen
Rijksuniversiteit Groningen
van Bokhoven, Hans
Netherlands, Nijmegen
Radboud University Medical Center
Körner, Christian
Austria, Vienna
Gottfried V Preyer Kinderspital
Babović-Vuksanović, Dusica
United States, Rochester
Mayo Clinic
Willemsen, M. A.A.P.
Netherlands, Nijmegen
Donders Institute for Brain, Cognition and Behaviour
Gleeson, Joseph G.
United States, La Jolla
Department of Neurosciences
Lehle, Ludwig
Germany, Regensburg
Universität Regensburg
de Brouwer, Arjan P.M.
Netherlands, Nijmegen
Radboud University Medical Center
Lefeber, Dirk J.
Netherlands, Nijmegen
Radboud University Medical Center
Netherlands, Nijmegen
Donders Institute for Brain, Cognition and Behaviour
Statistics
Citations: 92
Authors: 25
Affiliations: 11
Identifiers
Doi:
10.1093/brain/awq261
e-ISSN:
14602156
Research Areas
Genetics And Genomics
Health System And Policy
Noncommunicable Diseases