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Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3

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Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3. / Kornak, Uwe; Mademan, Inès; Schinke, Marte; Voigt, Martin; Krawitz, Peter; Hecht, Jochen; Barvencik, Florian; Schinke, Thorsten; Gießelmann, Sebastian; Beil, F Timo; Pou-Serradell, Adolf; Vílchez, Juan J; Beetz, Christian; Deconinck, Tine; Timmerman, Vincent; Kaether, Christoph; De Jonghe, Peter; Hübner, Christian A; Gal, Andreas; Amling, Michael; Mundlos, Stefan; Baets, Jonathan; Kurth, Ingo.

In: BRAIN, Vol. 137, No. 3, 01.03.2014, p. 683-92.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kornak, U, Mademan, I, Schinke, M, Voigt, M, Krawitz, P, Hecht, J, Barvencik, F, Schinke, T, Gießelmann, S, Beil, FT, Pou-Serradell, A, Vílchez, JJ, Beetz, C, Deconinck, T, Timmerman, V, Kaether, C, De Jonghe, P, Hübner, CA, Gal, A, Amling, M, Mundlos, S, Baets, J & Kurth, I 2014, 'Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3', BRAIN, vol. 137, no. 3, pp. 683-92. https://doi.org/10.1093/brain/awt357

APA

Kornak, U., Mademan, I., Schinke, M., Voigt, M., Krawitz, P., Hecht, J., Barvencik, F., Schinke, T., Gießelmann, S., Beil, F. T., Pou-Serradell, A., Vílchez, J. J., Beetz, C., Deconinck, T., Timmerman, V., Kaether, C., De Jonghe, P., Hübner, C. A., Gal, A., ... Kurth, I. (2014). Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3. BRAIN, 137(3), 683-92. https://doi.org/10.1093/brain/awt357

Vancouver

Kornak U, Mademan I, Schinke M, Voigt M, Krawitz P, Hecht J et al. Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3. BRAIN. 2014 Mar 1;137(3):683-92. https://doi.org/10.1093/brain/awt357

Bibtex

@article{c1f62253592740e391555163860fc784,
title = "Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3",
abstract = "Many neurodegenerative disorders present with sensory loss. In the group of hereditary sensory and autonomic neuropathies loss of nociception is one of the disease hallmarks. To determine underlying factors of sensory neurodegeneration we performed whole-exome sequencing in affected individuals with the disorder. In a family with sensory neuropathy with loss of pain perception and destruction of the pedal skeleton we report a missense mutation in a highly conserved amino acid residue of atlastin GTPase 3 (ATL3), an endoplasmic reticulum-shaping GTPase. The same mutation (p.Tyr192Cys) was identified in a second family with similar clinical outcome by screening a large cohort of 115 patients with hereditary sensory and autonomic neuropathies. Both families show an autosomal dominant pattern of inheritance and the mutation segregates with complete penetrance. ATL3 is a paralogue of ATL1, a membrane curvature-generating molecule that is involved in spastic paraplegia and hereditary sensory neuropathy. ATL3 proteins are enriched in three-way junctions, branch points of the endoplasmic reticulum that connect membranous tubules to a continuous network. Mutant ATL3 p.Tyr192Cys fails to localize to branch points, but instead disrupts the structure of the tubular endoplasmic reticulum, suggesting that the mutation exerts a dominant-negative effect. Identification of ATL3 as novel disease-associated gene exemplifies that long-term sensory neuronal maintenance critically depends on the structural organisation of the endoplasmic reticulum. It emphasizes that alterations in membrane shaping-proteins are one of the major emerging pathways in axonal degeneration and suggests that this group of molecules should be considered in neuroprotective strategies.",
keywords = "Adult, Age of Onset, Bone Diseases, Cohort Studies, Cough, Endoplasmic Reticulum, Exome, Female, Fractures, Bone, GTP Phosphohydrolases, Gastroesophageal Reflux, Genes, Dominant, Haplotypes, Hereditary Sensory and Autonomic Neuropathies, Humans, Intracellular Space, Male, Mutation, Mutation, Missense, Pedigree, Phenotype, Young Adult",
author = "Uwe Kornak and In{\`e}s Mademan and Marte Schinke and Martin Voigt and Peter Krawitz and Jochen Hecht and Florian Barvencik and Thorsten Schinke and Sebastian Gie{\ss}elmann and Beil, {F Timo} and Adolf Pou-Serradell and V{\'i}lchez, {Juan J} and Christian Beetz and Tine Deconinck and Vincent Timmerman and Christoph Kaether and {De Jonghe}, Peter and H{\"u}bner, {Christian A} and Andreas Gal and Michael Amling and Stefan Mundlos and Jonathan Baets and Ingo Kurth",
year = "2014",
month = mar,
day = "1",
doi = "10.1093/brain/awt357",
language = "English",
volume = "137",
pages = "683--92",
journal = "BRAIN",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "3",

}

RIS

TY - JOUR

T1 - Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3

AU - Kornak, Uwe

AU - Mademan, Inès

AU - Schinke, Marte

AU - Voigt, Martin

AU - Krawitz, Peter

AU - Hecht, Jochen

AU - Barvencik, Florian

AU - Schinke, Thorsten

AU - Gießelmann, Sebastian

AU - Beil, F Timo

AU - Pou-Serradell, Adolf

AU - Vílchez, Juan J

AU - Beetz, Christian

AU - Deconinck, Tine

AU - Timmerman, Vincent

AU - Kaether, Christoph

AU - De Jonghe, Peter

AU - Hübner, Christian A

AU - Gal, Andreas

AU - Amling, Michael

AU - Mundlos, Stefan

AU - Baets, Jonathan

AU - Kurth, Ingo

PY - 2014/3/1

Y1 - 2014/3/1

N2 - Many neurodegenerative disorders present with sensory loss. In the group of hereditary sensory and autonomic neuropathies loss of nociception is one of the disease hallmarks. To determine underlying factors of sensory neurodegeneration we performed whole-exome sequencing in affected individuals with the disorder. In a family with sensory neuropathy with loss of pain perception and destruction of the pedal skeleton we report a missense mutation in a highly conserved amino acid residue of atlastin GTPase 3 (ATL3), an endoplasmic reticulum-shaping GTPase. The same mutation (p.Tyr192Cys) was identified in a second family with similar clinical outcome by screening a large cohort of 115 patients with hereditary sensory and autonomic neuropathies. Both families show an autosomal dominant pattern of inheritance and the mutation segregates with complete penetrance. ATL3 is a paralogue of ATL1, a membrane curvature-generating molecule that is involved in spastic paraplegia and hereditary sensory neuropathy. ATL3 proteins are enriched in three-way junctions, branch points of the endoplasmic reticulum that connect membranous tubules to a continuous network. Mutant ATL3 p.Tyr192Cys fails to localize to branch points, but instead disrupts the structure of the tubular endoplasmic reticulum, suggesting that the mutation exerts a dominant-negative effect. Identification of ATL3 as novel disease-associated gene exemplifies that long-term sensory neuronal maintenance critically depends on the structural organisation of the endoplasmic reticulum. It emphasizes that alterations in membrane shaping-proteins are one of the major emerging pathways in axonal degeneration and suggests that this group of molecules should be considered in neuroprotective strategies.

AB - Many neurodegenerative disorders present with sensory loss. In the group of hereditary sensory and autonomic neuropathies loss of nociception is one of the disease hallmarks. To determine underlying factors of sensory neurodegeneration we performed whole-exome sequencing in affected individuals with the disorder. In a family with sensory neuropathy with loss of pain perception and destruction of the pedal skeleton we report a missense mutation in a highly conserved amino acid residue of atlastin GTPase 3 (ATL3), an endoplasmic reticulum-shaping GTPase. The same mutation (p.Tyr192Cys) was identified in a second family with similar clinical outcome by screening a large cohort of 115 patients with hereditary sensory and autonomic neuropathies. Both families show an autosomal dominant pattern of inheritance and the mutation segregates with complete penetrance. ATL3 is a paralogue of ATL1, a membrane curvature-generating molecule that is involved in spastic paraplegia and hereditary sensory neuropathy. ATL3 proteins are enriched in three-way junctions, branch points of the endoplasmic reticulum that connect membranous tubules to a continuous network. Mutant ATL3 p.Tyr192Cys fails to localize to branch points, but instead disrupts the structure of the tubular endoplasmic reticulum, suggesting that the mutation exerts a dominant-negative effect. Identification of ATL3 as novel disease-associated gene exemplifies that long-term sensory neuronal maintenance critically depends on the structural organisation of the endoplasmic reticulum. It emphasizes that alterations in membrane shaping-proteins are one of the major emerging pathways in axonal degeneration and suggests that this group of molecules should be considered in neuroprotective strategies.

KW - Adult

KW - Age of Onset

KW - Bone Diseases

KW - Cohort Studies

KW - Cough

KW - Endoplasmic Reticulum

KW - Exome

KW - Female

KW - Fractures, Bone

KW - GTP Phosphohydrolases

KW - Gastroesophageal Reflux

KW - Genes, Dominant

KW - Haplotypes

KW - Hereditary Sensory and Autonomic Neuropathies

KW - Humans

KW - Intracellular Space

KW - Male

KW - Mutation

KW - Mutation, Missense

KW - Pedigree

KW - Phenotype

KW - Young Adult

U2 - 10.1093/brain/awt357

DO - 10.1093/brain/awt357

M3 - SCORING: Journal article

C2 - 24459106

VL - 137

SP - 683

EP - 692

JO - BRAIN

JF - BRAIN

SN - 0006-8950

IS - 3

ER -