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Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. / Namavar, Yasmin; Barth, Peter G.; Kasher, Paul R. et al.

In: Brain, Vol. 134, No. Part 1, 2011, p. 143-156.

Research output: Contribution to journal › Article › Academic › peer-review

Harvard

Namavar, Y, Barth, PG, Kasher, PR, van Ruissen, F, Brockmann, K, Bernert, G, Writzl, K, Ventura, K, Cheng, EY, Ferriero, DM, Basel-Vanagaite, L, Eggens, VRC, Krägeloh-Mann, I, de Meirleir, L, King, M, Graham, JM, von Moers, A, Knoers, N, Sztriha, L, Korinthenberg, R, Dobyns, WB, Baas, F, Poll-The, BT & AUTHOR GROUP 2011, 'Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia', Brain, vol. 134, no. Part 1, pp. 143-156. https://doi.org/10.1093/brain/awq287

APA

Namavar, Y., Barth, P. G., Kasher, P. R., van Ruissen, F., Brockmann, K., Bernert, G., Writzl, K., Ventura, K., Cheng, E. Y., Ferriero, D. M., Basel-Vanagaite, L., Eggens, V. R. C., Krägeloh-Mann, I., de Meirleir, L., King, M., Graham, J. M., von Moers, A., Knoers, N., Sztriha, L., ... AUTHOR GROUP (2011). Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. Brain, 134(Part 1), 143-156. https://doi.org/10.1093/brain/awq287

Vancouver

Namavar Y, Barth PG, Kasher PR, van Ruissen F, Brockmann K, Bernert G et al. Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. Brain. 2011;134(Part 1):143-156. doi: 10.1093/brain/awq287

Author

Namavar, Yasmin ; Barth, Peter G. ; Kasher, Paul R. et al. / Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. In: Brain. 2011 ; Vol. 134, No. Part 1. pp. 143-156.

BibTeX

@article{983f623e9f324cebb2a5ee5187f710ba,
title = "Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia",
abstract = "Pontocerebellar hypoplasia is a group of autosomal recessive neurodegenerative disorders with prenatal onset. The common characteristics are cerebellar hypoplasia with variable atrophy of the cerebellum and the ventral pons. Supratentorial involvement is reflected by variable neocortical atrophy, ventriculomegaly and microcephaly. Mutations in the transfer RNA splicing endonuclease subunit genes (TSEN54, TSEN2, TSEN34) were found to be associated with pontocerebellar hypoplasia types 2 and 4. Mutations in the mitochondrial transfer RNA arginyl synthetase gene (RARS2) were associated with pontocerebellar hypoplasia type 6. We studied a cohort of 169 patients from 141 families for mutations in these genes, of whom 106 patients tested positive for mutations in one of the TSEN genes or the RARS2 gene. In order to delineate the neuroradiological and clinical phenotype of patients with mutations in these genes, we compared this group with 63 patients suspected of pontocerebellar hypoplasia who were negative on mutation analysis. We found a strong correlation (P <0.0005) between TSEN54 mutations and a dragonfly-like cerebellar pattern on magnetic resonance imaging, in which the cerebellar hemispheres are flat and severely reduced in size and the vermis is relatively spared. Mutations in TSEN54 are clinically associated with dyskinesia and/or dystonia and variable degrees of spasticity, in some cases with pure generalized spasticity. Nonsense or splice site mutations in TSEN54 are associated with a more severe phenotype of more perinatal symptoms, ventilator dependency and early death. In addition, we present ten new mutations in TSEN54, TSEN2 and RARS2. Furthermore, we show that pontocerebellar hypoplasia type 1 together with elevated cerebrospinal fluid lactate may be caused by RARS2 mutations",
author = "Yasmin Namavar and Barth, {Peter G.} and Kasher, {Paul R.} and {van Ruissen}, Fred and Knut Brockmann and G{\"u}nther Bernert and Karin Writzl and Karen Ventura and Cheng, {Edith Y.} and Ferriero, {Donna M.} and Lina Basel-Vanagaite and Eggens, {Veerle R. C.} and Ingeborg Kr{\"a}geloh-Mann and {de Meirleir}, Linda and Mary King and Graham, {John M.} and {von Moers}, Arpad and Nine Knoers and Laszlo Sztriha and Rudolf Korinthenberg and Dobyns, {William B.} and Frank Baas and Poll-The, {Bwee Tien} and {AUTHOR GROUP} and {van der Aa}, Nathalie and Arts, {Willem F. M.} and Ades, {Lesley C.} and Nadia Bahi-Buisson and Roberta Battini and Olaf Bodamer and Eugen Boltshauser and Kym Boycott and Louise Brueton and Wim Brussel and Chandler, {K. E.} and Cowan, {Frances M.} and Yanick Crow and Otfried Debus and Ercan Demir and Gazi Hastanesi and Jacqueline Eason and Ferrie, {Colin D.} and Fisher, {Richard B.} and Nicola Foulds and Freeman, {Jeremy L.} and Rob Gooskens and Martin Haeussler and Gerard Hageman and Gerhard Hammersen and Denise Horn and Tijssen, {Marina A. J.}",
year = "2011",
doi = "10.1093/brain/awq287",
language = "English",
volume = "134",
pages = "143--156",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "Part 1",

}

RIS

TY - JOUR

T1 - Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia

AU - Namavar, Yasmin

AU - Barth, Peter G.

AU - Kasher, Paul R.

AU - van Ruissen, Fred

AU - Brockmann, Knut

AU - Bernert, Günther

AU - Writzl, Karin

AU - Ventura, Karen

AU - Cheng, Edith Y.

AU - Ferriero, Donna M.

AU - Basel-Vanagaite, Lina

AU - Eggens, Veerle R. C.

AU - Krägeloh-Mann, Ingeborg

AU - de Meirleir, Linda

AU - King, Mary

AU - Graham, John M.

AU - von Moers, Arpad

AU - Knoers, Nine

AU - Sztriha, Laszlo

AU - Korinthenberg, Rudolf

AU - Dobyns, William B.

AU - Baas, Frank

AU - Poll-The, Bwee Tien

AU - AUTHOR GROUP

AU - van der Aa, Nathalie

AU - Arts, Willem F. M.

AU - Ades, Lesley C.

AU - Bahi-Buisson, Nadia

AU - Battini, Roberta

AU - Bodamer, Olaf

AU - Boltshauser, Eugen

AU - Boycott, Kym

AU - Brueton, Louise

AU - Brussel, Wim

AU - Chandler, K. E.

AU - Cowan, Frances M.

AU - Crow, Yanick

AU - Debus, Otfried

AU - Demir, Ercan

AU - Hastanesi, Gazi

AU - Eason, Jacqueline

AU - Ferrie, Colin D.

AU - Fisher, Richard B.

AU - Foulds, Nicola

AU - Freeman, Jeremy L.

AU - Gooskens, Rob

AU - Haeussler, Martin

AU - Hageman, Gerard

AU - Hammersen, Gerhard

AU - Horn, Denise

AU - Tijssen, Marina A. J.

PY - 2011

Y1 - 2011

N2 - Pontocerebellar hypoplasia is a group of autosomal recessive neurodegenerative disorders with prenatal onset. The common characteristics are cerebellar hypoplasia with variable atrophy of the cerebellum and the ventral pons. Supratentorial involvement is reflected by variable neocortical atrophy, ventriculomegaly and microcephaly. Mutations in the transfer RNA splicing endonuclease subunit genes (TSEN54, TSEN2, TSEN34) were found to be associated with pontocerebellar hypoplasia types 2 and 4. Mutations in the mitochondrial transfer RNA arginyl synthetase gene (RARS2) were associated with pontocerebellar hypoplasia type 6. We studied a cohort of 169 patients from 141 families for mutations in these genes, of whom 106 patients tested positive for mutations in one of the TSEN genes or the RARS2 gene. In order to delineate the neuroradiological and clinical phenotype of patients with mutations in these genes, we compared this group with 63 patients suspected of pontocerebellar hypoplasia who were negative on mutation analysis. We found a strong correlation (P <0.0005) between TSEN54 mutations and a dragonfly-like cerebellar pattern on magnetic resonance imaging, in which the cerebellar hemispheres are flat and severely reduced in size and the vermis is relatively spared. Mutations in TSEN54 are clinically associated with dyskinesia and/or dystonia and variable degrees of spasticity, in some cases with pure generalized spasticity. Nonsense or splice site mutations in TSEN54 are associated with a more severe phenotype of more perinatal symptoms, ventilator dependency and early death. In addition, we present ten new mutations in TSEN54, TSEN2 and RARS2. Furthermore, we show that pontocerebellar hypoplasia type 1 together with elevated cerebrospinal fluid lactate may be caused by RARS2 mutations

AB - Pontocerebellar hypoplasia is a group of autosomal recessive neurodegenerative disorders with prenatal onset. The common characteristics are cerebellar hypoplasia with variable atrophy of the cerebellum and the ventral pons. Supratentorial involvement is reflected by variable neocortical atrophy, ventriculomegaly and microcephaly. Mutations in the transfer RNA splicing endonuclease subunit genes (TSEN54, TSEN2, TSEN34) were found to be associated with pontocerebellar hypoplasia types 2 and 4. Mutations in the mitochondrial transfer RNA arginyl synthetase gene (RARS2) were associated with pontocerebellar hypoplasia type 6. We studied a cohort of 169 patients from 141 families for mutations in these genes, of whom 106 patients tested positive for mutations in one of the TSEN genes or the RARS2 gene. In order to delineate the neuroradiological and clinical phenotype of patients with mutations in these genes, we compared this group with 63 patients suspected of pontocerebellar hypoplasia who were negative on mutation analysis. We found a strong correlation (P <0.0005) between TSEN54 mutations and a dragonfly-like cerebellar pattern on magnetic resonance imaging, in which the cerebellar hemispheres are flat and severely reduced in size and the vermis is relatively spared. Mutations in TSEN54 are clinically associated with dyskinesia and/or dystonia and variable degrees of spasticity, in some cases with pure generalized spasticity. Nonsense or splice site mutations in TSEN54 are associated with a more severe phenotype of more perinatal symptoms, ventilator dependency and early death. In addition, we present ten new mutations in TSEN54, TSEN2 and RARS2. Furthermore, we show that pontocerebellar hypoplasia type 1 together with elevated cerebrospinal fluid lactate may be caused by RARS2 mutations

U2 - 10.1093/brain/awq287

DO - 10.1093/brain/awq287

M3 - Article

C2 - 20952379

VL - 134

SP - 143

EP - 156

JO - Brain

JF - Brain

SN - 0006-8950

IS - Part 1

ER -

ID: 1331710