The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Erik T. Te Beek - One of the best experts on this subject based on the ideXlab platform.
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tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
Nature Genetics, 2008Co-Authors: Birgit Budde, Yasmin Namavar, Peter G. Barth, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Gudrun Nurnberg, Christian Becker, Bwee Tien Poll-the, Erik T. Te BeekAbstract:Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders. Frank Baas and colleagues report mutations in three of the four subunits of the tRNA-splicing endonuclease complex in families with two subtypes of pontocerebellar hypoplasia. The findings implicate tRNA processing in neurological disorders.
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tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
Nature Genetics, 2008Co-Authors: Birgit Budde, Yasmin Namavar, Peter G. Barth, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Gudrun Nurnberg, Christian Becker, Bwee Tien Poll-the, Erik T. Te BeekAbstract:Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.
Peter G. Barth - One of the best experts on this subject based on the ideXlab platform.
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Ectopic peripontine arcuate fibres, a novel finding in pontine tegmental cap dysplasia
European Journal of Paediatric Neurology, 2014Co-Authors: Matthan W.a. Caan, Peter G. Barth, Jikke-mien Niermeijer, Charles B. L. M. Majoie, Bwee Tien Poll-theAbstract:Abstract Background Pontine Tegmental Cap Dysplasia (PTCD) is a recently described hindbrain malformation presenting hypoplasia of the Ventral Pons, and a “pontine tegmental cap”. Previous DTI studies identified ectopic transversely oriented nerve fibres in the cap, and absence of transverse fibre bundles in the Ventral Pons, characterizing PTCD as an embryonic axon guidance defect. A new case with relatively mild symptoms was investigated to identify fibre tracts in the tegmental cap by tracking their connections. In the process a new bilateral ectopic fibre tract was found. Methods Routine T1- and T2 weighted images and Diffusion Tensor Imaging (DTI) data were obtained on a 3 T MR scanner. Fractional Anisotropy maps colour coded for orientation were generated. High Angular Resolution Diffusion Imaging (HARDI) data were used for reconstructing maps denoting multiple fibre orientations (i.e. fibre crossings) per voxel through which accurate fibre tracking was performed. Results 1. A pontine tegmental cap was discovered on routine MRI and shown to carry transverse oriented fibres on DTI as in previously reported cases of PTCD. 2. A new finding revealed by DTI with colour coding and fibre tracking, was a robust midline bundle, traced back to the lower brainstem, that ended rostrally in two semi-arcuate loops skirting the outer margins of the Pons, to connect to the cerebellar hemispheres close to but outside the middle cerebellar peduncles. Part of this fibre tract was detectable on routine MRI. Interpretation Peripontine arcuate fibres were identified, representing a second structural abnormality not previously recorded in PTCD.
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Mutations of TSEN and CASK genes are prevalent in pontocerebellar hypoplasias type 2 and 4
Brain, 2011Co-Authors: Yasmin Namavar, Peter G. Barth, Frank Baas, Bwee Tien Poll-theAbstract:Sir, Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments (Barth, 2000). Recently in two subtypes, PCH type 2 (associated with dyskinesia and/or dystonia and variable degrees of spasticity) and PCH type 4 (a more severe phenotype associated with perinatal symptoms, ventilator dependency and early death), mutations have been identified in three of the four different subunits of the transfer RNA-splicing endonuclease complex ( TSEN54 , TSEN34 and TSEN2 ) (Budde et al. , 2008). Mutations in the calcium/calmodulin-dependent serine protein kinase ( CASK ) gene have also been associated with X-linked mental retardation (XLMR) with microcephaly, optic atrophy and brainstem and cerebellar hypoplasia (Najm et al. , 2008). Namavar et al. (2011) reported on a series of 169 patients affected with PCH and identified mutations in TSEN54 or RARS2 genes in 106 individuals. The authors display a strong correlation 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. They also show that homozygosity for the common …
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tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
Nature Genetics, 2008Co-Authors: Birgit Budde, Yasmin Namavar, Peter G. Barth, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Gudrun Nurnberg, Christian Becker, Bwee Tien Poll-the, Erik T. Te BeekAbstract:Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders. Frank Baas and colleagues report mutations in three of the four subunits of the tRNA-splicing endonuclease complex in families with two subtypes of pontocerebellar hypoplasia. The findings implicate tRNA processing in neurological disorders.
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tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
Nature Genetics, 2008Co-Authors: Birgit Budde, Yasmin Namavar, Peter G. Barth, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Gudrun Nurnberg, Christian Becker, Bwee Tien Poll-the, Erik T. Te BeekAbstract:Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.
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Congenital brainstem disconnection associated with a syrinx of the brainstem.
Neuropediatrics, 2008Co-Authors: Peter G. Barth, L. S. De Vries, Peter G.j. Nikkels, Dirk TroostAbstract:We report a case of congenital brainstem disconnection including the second detailed autopsy. A full-term newborn presented with irreversible apnoea and died on the fifth day. MRI revealed disconnection of the brainstem. The autopsy included a series of transverse sections of the mesencephalon, medulla oblongata and bridging tissue fragments. A fragile tube walled by mature brainstem tissue could be reconstructed. It enveloped a cylinder of fluid within the Ventral Pons extending to the mesencephalon and the lower brainstem. The aqueduct was patent and outside the lesion. The basilar artery was represented by a tiny median vessel. The Ventral and lateral parts of the posterior brainstem were surrounded by heterotopic glial tissue. The olivary nucleus was absent and the cerebellar dentate nucleus was dysplastic. Considering the maturity of the remaining parts of the Pons, the onset of structural decline is likely to be close to the time of birth. Probable causes are progressively insufficient perfusion through an hypoplastic basilar artery, and obstructed venous drainage through an abnormal glial barrier surrounding the posterior brainstem. The morphological findings can be characterized as a syrinx, known from disorders in which brainstem or spinal cord are damaged by a combination of mechanical and circulatory factors.
Bwee Tien Poll-the - One of the best experts on this subject based on the ideXlab platform.
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Ectopic peripontine arcuate fibres, a novel finding in pontine tegmental cap dysplasia
European Journal of Paediatric Neurology, 2014Co-Authors: Matthan W.a. Caan, Peter G. Barth, Jikke-mien Niermeijer, Charles B. L. M. Majoie, Bwee Tien Poll-theAbstract:Abstract Background Pontine Tegmental Cap Dysplasia (PTCD) is a recently described hindbrain malformation presenting hypoplasia of the Ventral Pons, and a “pontine tegmental cap”. Previous DTI studies identified ectopic transversely oriented nerve fibres in the cap, and absence of transverse fibre bundles in the Ventral Pons, characterizing PTCD as an embryonic axon guidance defect. A new case with relatively mild symptoms was investigated to identify fibre tracts in the tegmental cap by tracking their connections. In the process a new bilateral ectopic fibre tract was found. Methods Routine T1- and T2 weighted images and Diffusion Tensor Imaging (DTI) data were obtained on a 3 T MR scanner. Fractional Anisotropy maps colour coded for orientation were generated. High Angular Resolution Diffusion Imaging (HARDI) data were used for reconstructing maps denoting multiple fibre orientations (i.e. fibre crossings) per voxel through which accurate fibre tracking was performed. Results 1. A pontine tegmental cap was discovered on routine MRI and shown to carry transverse oriented fibres on DTI as in previously reported cases of PTCD. 2. A new finding revealed by DTI with colour coding and fibre tracking, was a robust midline bundle, traced back to the lower brainstem, that ended rostrally in two semi-arcuate loops skirting the outer margins of the Pons, to connect to the cerebellar hemispheres close to but outside the middle cerebellar peduncles. Part of this fibre tract was detectable on routine MRI. Interpretation Peripontine arcuate fibres were identified, representing a second structural abnormality not previously recorded in PTCD.
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Mutations of TSEN and CASK genes are prevalent in pontocerebellar hypoplasias type 2 and 4
Brain, 2011Co-Authors: Yasmin Namavar, Peter G. Barth, Frank Baas, Bwee Tien Poll-theAbstract:Sir, Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments (Barth, 2000). Recently in two subtypes, PCH type 2 (associated with dyskinesia and/or dystonia and variable degrees of spasticity) and PCH type 4 (a more severe phenotype associated with perinatal symptoms, ventilator dependency and early death), mutations have been identified in three of the four different subunits of the transfer RNA-splicing endonuclease complex ( TSEN54 , TSEN34 and TSEN2 ) (Budde et al. , 2008). Mutations in the calcium/calmodulin-dependent serine protein kinase ( CASK ) gene have also been associated with X-linked mental retardation (XLMR) with microcephaly, optic atrophy and brainstem and cerebellar hypoplasia (Najm et al. , 2008). Namavar et al. (2011) reported on a series of 169 patients affected with PCH and identified mutations in TSEN54 or RARS2 genes in 106 individuals. The authors display a strong correlation 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. They also show that homozygosity for the common …
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tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
Nature Genetics, 2008Co-Authors: Birgit Budde, Yasmin Namavar, Peter G. Barth, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Gudrun Nurnberg, Christian Becker, Bwee Tien Poll-the, Erik T. Te BeekAbstract:Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders. Frank Baas and colleagues report mutations in three of the four subunits of the tRNA-splicing endonuclease complex in families with two subtypes of pontocerebellar hypoplasia. The findings implicate tRNA processing in neurological disorders.
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tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
Nature Genetics, 2008Co-Authors: Birgit Budde, Yasmin Namavar, Peter G. Barth, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Gudrun Nurnberg, Christian Becker, Bwee Tien Poll-the, Erik T. Te BeekAbstract:Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.
Birgit Budde - One of the best experts on this subject based on the ideXlab platform.
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tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
Nature Genetics, 2008Co-Authors: Birgit Budde, Yasmin Namavar, Peter G. Barth, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Gudrun Nurnberg, Christian Becker, Bwee Tien Poll-the, Erik T. Te BeekAbstract:Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders. Frank Baas and colleagues report mutations in three of the four subunits of the tRNA-splicing endonuclease complex in families with two subtypes of pontocerebellar hypoplasia. The findings implicate tRNA processing in neurological disorders.
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tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
Nature Genetics, 2008Co-Authors: Birgit Budde, Yasmin Namavar, Peter G. Barth, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Gudrun Nurnberg, Christian Becker, Bwee Tien Poll-the, Erik T. Te BeekAbstract:Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.
Marian A. J. Weterman - One of the best experts on this subject based on the ideXlab platform.
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tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
Nature Genetics, 2008Co-Authors: Birgit Budde, Yasmin Namavar, Peter G. Barth, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Gudrun Nurnberg, Christian Becker, Bwee Tien Poll-the, Erik T. Te BeekAbstract:Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders. Frank Baas and colleagues report mutations in three of the four subunits of the tRNA-splicing endonuclease complex in families with two subtypes of pontocerebellar hypoplasia. The findings implicate tRNA processing in neurological disorders.
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tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
Nature Genetics, 2008Co-Authors: Birgit Budde, Yasmin Namavar, Peter G. Barth, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Gudrun Nurnberg, Christian Becker, Bwee Tien Poll-the, Erik T. Te BeekAbstract:Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the Ventral Pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.
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Pontine tegmental cap dysplasia: a novel brain malformation with a defect in axonal guidance.
Brain, 2007Co-Authors: Peter G. Barth, Marian A. J. Weterman, Frank Baas, Charles B. Majoie, Matthan W.a. Caan, Marten Kyllerman, Leo M. E. Smit, Richard A. Kaplan, Richard H. Haas, J.m. CobbenAbstract:Four unrelated children are described with an identical brainstem and cerebellar malformation on MRI. The key findings are: vermal hypoplasia, subtotal absence of middle cerebellar peduncles, flattened Ventral Pons, vaulted pontine tegmentum, molar tooth aspect of the pontomesencephalic junction and absent inferior olivary prominence. Peripheral hearing impairment is present in all. Variable findings are: horizontal gaze palsy (1/4), impaired swallowing (2/4), facial palsy (3/4), bilateral sensory trigeminal nerve involvement (1/4), ataxia (2/4). Bony vertebral anomalies are found in 3/4. Additional MR studies in one patient using diffusion tensor imaging (DTI) with colour coding and fibre tracking revealed an ectopic transverse fibre bundle at the site of the pontine tegmentum and complete absence of transverse fibres in the Ventral Pons. The combined findings indicate an embryonic defect in axonal growth and guidance. Phenotypic analogy to mice with homozygous inactivation of Ntn1 encoding the secreted axonal guidance protein netrin1, or Dcc encoding its receptor Deleted in Colorectal Cancer led us to perform sequence analysis of NTN1 and DCC in all the patients. No pathogenic mutations were found. For the purpose of description the name ‘pontine tegmental cap dysplasia’ (PTCD) is proposed for the present malformation, referring to its most distinguishing feature on routine MRI.
