Publication

A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism

Morava, E., Wevers, R. A., Cantagrel, V., Hoefsloot, L. H., Al-Gazali, L., Schoots, J., van Rooij, A., Huijben, K., van Ravenswaaij-Arts, C. M. A., Jongmans, M. C. J., Sykut-Cegielska, J., Hoffmann, G. F., Bluemel, P., Adamowicz, M., van Reeuwijk, J., Ng, B. G., Bergman, J. E. H., van Bokhoven, H., Koerner, C., Babovic-Vuksanovic, D., Willemsen, M. A., Gleeson, J. G., Lehle, L., de Brouwer, A. P. M. & Lefeber, D. J., Nov-2010, In : Brain. 133, p. 3210-3220 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Morava, E., Wevers, R. A., Cantagrel, V., Hoefsloot, L. H., Al-Gazali, L., Schoots, J., ... Lefeber, D. J. (2010). A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism. Brain, 133, 3210-3220. https://doi.org/10.1093/brain/awq261

Author

Morava, Eva ; Wevers, Ron A. ; Cantagrel, Vincent ; Hoefsloot, Lies H. ; Al-Gazali, Lihadh ; Schoots, Jeroen ; van Rooij, Arno ; Huijben, Karin ; van Ravenswaaij-Arts, Connie M. A. ; Jongmans, Marjolein C. J. ; Sykut-Cegielska, Jolanta ; Hoffmann, Georg F. ; Bluemel, Peter ; Adamowicz, Maciej ; van Reeuwijk, Jeroen ; Ng, Bobby G. ; Bergman, Jorieke E. H. ; van Bokhoven, Hans ; Koerner, Christian ; Babovic-Vuksanovic, Dusica ; Willemsen, Michel A. ; Gleeson, Joseph G. ; Lehle, Ludwig ; de Brouwer, Arjan P. M. ; Lefeber, Dirk J. / A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism. In: Brain. 2010 ; Vol. 133. pp. 3210-3220.

Harvard

Morava, E, Wevers, RA, Cantagrel, V, Hoefsloot, LH, Al-Gazali, L, Schoots, J, van Rooij, A, Huijben, K, van Ravenswaaij-Arts, CMA, Jongmans, MCJ, Sykut-Cegielska, J, Hoffmann, GF, Bluemel, P, Adamowicz, M, van Reeuwijk, J, Ng, BG, Bergman, JEH, van Bokhoven, H, Koerner, C, Babovic-Vuksanovic, D, Willemsen, MA, Gleeson, JG, Lehle, L, de Brouwer, APM & Lefeber, DJ 2010, 'A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism', Brain, vol. 133, pp. 3210-3220. https://doi.org/10.1093/brain/awq261

Standard

A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism. / Morava, Eva; Wevers, Ron A.; Cantagrel, Vincent; Hoefsloot, Lies H.; Al-Gazali, Lihadh; Schoots, Jeroen; van Rooij, Arno; Huijben, Karin; van Ravenswaaij-Arts, Connie M. A.; Jongmans, Marjolein C. J.; Sykut-Cegielska, Jolanta; Hoffmann, Georg F.; Bluemel, Peter; Adamowicz, Maciej; van Reeuwijk, Jeroen; Ng, Bobby G.; Bergman, Jorieke E. H.; van Bokhoven, Hans; Koerner, Christian; Babovic-Vuksanovic, Dusica; Willemsen, Michel A.; Gleeson, Joseph G.; Lehle, Ludwig; de Brouwer, Arjan P. M.; Lefeber, Dirk J.

In: Brain, Vol. 133, 11.2010, p. 3210-3220.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Morava E, Wevers RA, Cantagrel V, Hoefsloot LH, Al-Gazali L, Schoots J et al. A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism. Brain. 2010 Nov;133:3210-3220. https://doi.org/10.1093/brain/awq261


BibTeX

@article{20d9c0de85324d3ab26ca83513ba7624,
title = "A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism",
abstract = "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 5 alpha-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 5 alpha-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.",
keywords = "congenital disorders of glycosylation, SRD5A3-CDG, CDG type Iq, glycosylation, dolichol metabolism, polyprenol reductase, SRD5A3, vermis hypoplasia, coloboma, cataract, glaucoma, AUTOSOMAL RECESSIVE SYNDROME, CONGENITAL DISORDERS, CHARGE-SYNDROME, MENTAL-RETARDATION, JOUBERT-SYNDROME, CDG, MUTATIONS, GENE, BIOSYNTHESIS, SPECTRUM",
author = "Eva Morava and Wevers, {Ron A.} and Vincent Cantagrel and Hoefsloot, {Lies H.} and Lihadh Al-Gazali and Jeroen Schoots and {van Rooij}, Arno and Karin Huijben and {van Ravenswaaij-Arts}, {Connie M. A.} and Jongmans, {Marjolein C. J.} and Jolanta Sykut-Cegielska and Hoffmann, {Georg F.} and Peter Bluemel and Maciej Adamowicz and {van Reeuwijk}, Jeroen and Ng, {Bobby G.} and Bergman, {Jorieke E. H.} and {van Bokhoven}, Hans and Christian Koerner and Dusica Babovic-Vuksanovic and Willemsen, {Michel A.} and Gleeson, {Joseph G.} and Ludwig Lehle and {de Brouwer}, {Arjan P. M.} and Lefeber, {Dirk J.}",
year = "2010",
month = "11",
doi = "10.1093/brain/awq261",
language = "English",
volume = "133",
pages = "3210--3220",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism

AU - Morava, Eva

AU - Wevers, Ron A.

AU - Cantagrel, Vincent

AU - Hoefsloot, Lies H.

AU - Al-Gazali, Lihadh

AU - Schoots, Jeroen

AU - van Rooij, Arno

AU - Huijben, Karin

AU - van Ravenswaaij-Arts, Connie M. A.

AU - Jongmans, Marjolein C. J.

AU - Sykut-Cegielska, Jolanta

AU - Hoffmann, Georg F.

AU - Bluemel, Peter

AU - Adamowicz, Maciej

AU - van Reeuwijk, Jeroen

AU - Ng, Bobby G.

AU - Bergman, Jorieke E. H.

AU - van Bokhoven, Hans

AU - Koerner, Christian

AU - Babovic-Vuksanovic, Dusica

AU - Willemsen, Michel A.

AU - Gleeson, Joseph G.

AU - Lehle, Ludwig

AU - de Brouwer, Arjan P. M.

AU - Lefeber, Dirk J.

PY - 2010/11

Y1 - 2010/11

N2 - 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 5 alpha-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 5 alpha-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.

AB - 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 5 alpha-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 5 alpha-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.

KW - congenital disorders of glycosylation

KW - SRD5A3-CDG

KW - CDG type Iq

KW - glycosylation

KW - dolichol metabolism

KW - polyprenol reductase

KW - SRD5A3

KW - vermis hypoplasia

KW - coloboma

KW - cataract

KW - glaucoma

KW - AUTOSOMAL RECESSIVE SYNDROME

KW - CONGENITAL DISORDERS

KW - CHARGE-SYNDROME

KW - MENTAL-RETARDATION

KW - JOUBERT-SYNDROME

KW - CDG

KW - MUTATIONS

KW - GENE

KW - BIOSYNTHESIS

KW - SPECTRUM

U2 - 10.1093/brain/awq261

DO - 10.1093/brain/awq261

M3 - Article

VL - 133

SP - 3210

EP - 3220

JO - Brain

JF - Brain

SN - 0006-8950

ER -

ID: 5196362