English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

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

Kornak, U., Mademan, I., Schinke, M., Voigt, M., Krawitz, P., Hecht, J., et al. (2014). Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3. Brain, 137(3), 683-692. doi:10.1093/brain/awt357.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-78D5-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-78D6-F
Genre: Journal Article

Files

show Files
hide Files
:
Kornak.pdf (Publisher version), 898KB
Name:
Kornak.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2014 Oxford University Press
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Kornak, U.1, Author              
Mademan, I., Author
Schinke, M., Author
Voigt, M., Author
Krawitz, P., Author
Hecht, J.1, Author              
Barvencik, F., Author
Schinke, T., Author
Giesselmann, S., Author
Beil, F. T., Author
Pou-Serradell, A., Author
Vilchez, J. J., Author
Beetz, C., Author
Deconinck, T., Author
Timmerman, V., Author
Kaether, C., Author
De Jonghe, P., Author
Hubner, C. A., Author
Gal, A., Author
Amling, M., Author
Mundlos, S.1, Author              Baets, J., AuthorKurth, I., Author more..
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

Content

show
hide
Free keywords: Adult Age of Onset Bone Diseases/etiology/*genetics/physiopathology Cohort Studies Cough/genetics/pathology/physiopathology Endoplasmic Reticulum/*genetics/pathology Exome/genetics Female Fractures, Bone/genetics/pathology GTP Phosphohydrolases/*genetics Gastroesophageal Reflux/genetics/pathology/physiopathology Genes, Dominant/genetics Haplotypes/genetics Hereditary Sensory and Autonomic Neuropathies/complications/*genetics/pathology/physiopathology Humans Intracellular Space/genetics Male Mutation Mutation, Missense/genetics Pedigree Phenotype Young Adult
 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.

Details

show
hide
Language(s): eng - English
 Dates: 2014-01-222014-03
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1093/brain/awt357
ISSN: 1460-2156 (Electronic)0006-8950 (Print)
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Brain
  Other : Brain
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London : Macmillan
Pages: - Volume / Issue: 137 (3) Sequence Number: - Start / End Page: 683 - 692 Identifier: ISSN: 0006-8950
CoNE: https://pure.mpg.de/cone/journals/resource/954925385135