The University of Southampton
University of Southampton Institutional Repository

Late-onset ptosis and myopathy in a patient with a heterozygous insertion in POLG2

Late-onset ptosis and myopathy in a patient with a heterozygous insertion in POLG2
Late-onset ptosis and myopathy in a patient with a heterozygous insertion in POLG2
Polymerase gamma 1 (POLG) mutations are a frequent cause of both autosomal dominant and recessive complex neurological phenotypes. In contrast, only a single pathogenic mutation in one patient was reported in POLG2 so far. Here we describe a 62-year-old woman, carrying a novel heterozygous sequence variant in the POLG2 gene. She developed bilateral ptosis at 30 years of age, followed by exercise intolerance, muscle weakness and mild CK increase in her late forties. Muscle histology and respiratory chain activities were normal. Southern blot and long range PCR detected multiple mtDNA deletions, but no depletion in muscle DNA. Sequencing of POLG, PEO1, ANT1, OPA1 and RRM2B showed normal results. A novel heteroallelic 24 bp insertion (c.1207_1208ins24) was detected in POLG2. This 24 bp insertion into exon 7 causes missplicing and loss of exon 7 in myoblast cDNA. We did not detect POLG2 mutations in 62 patients with multiple mtDNA deletions in muscle DNA, suggesting that POLG2 mutations may represent a rare cause of autosomal dominant PEO.
0340-5354
1517-1523
Walter, Maggie C
6364d233-1362-43b3-a750-68fc8da0a859
Czermin, Birgit
063e0cae-2c7a-4eb4-a30e-298465574336
Muller-Ziermann, Solvig
3a288c67-28f1-4ffb-86b4-b239296d761a
Bulst, Stefanie
33f45952-4959-48bc-9986-227087693bd2
Stewart, Joanna D
e1ec9784-39cc-48ed-9f4f-2a05d25f2106
Hudson, Gavin
cbad491d-cc7f-4bea-b214-b6752151fc13
Schneiderat, Peter
3af8453a-906b-4278-8323-20ec2f0e26ce
Abicht, Angela
8c9ac9fe-eb9f-40b2-8167-898c047532d1
Holinski-Feder, Elke
a11466cc-d92e-4398-89e2-d90d439c05c1
Lochmüller, Hanns
dbc374ba-28c4-43ef-a459-b131cf865894
Chinnery, Patrick F
87789d1a-5265-4815-9f11-194ed9b4ad94
Klopstock, Thomas
6f505e28-e765-4076-8ed2-48e67320f44f
Horvath, Rita
e41c9ffa-b0a0-4ebb-a44a-b98a2c6c23cd
Walter, Maggie C
6364d233-1362-43b3-a750-68fc8da0a859
Czermin, Birgit
063e0cae-2c7a-4eb4-a30e-298465574336
Muller-Ziermann, Solvig
3a288c67-28f1-4ffb-86b4-b239296d761a
Bulst, Stefanie
33f45952-4959-48bc-9986-227087693bd2
Stewart, Joanna D
e1ec9784-39cc-48ed-9f4f-2a05d25f2106
Hudson, Gavin
cbad491d-cc7f-4bea-b214-b6752151fc13
Schneiderat, Peter
3af8453a-906b-4278-8323-20ec2f0e26ce
Abicht, Angela
8c9ac9fe-eb9f-40b2-8167-898c047532d1
Holinski-Feder, Elke
a11466cc-d92e-4398-89e2-d90d439c05c1
Lochmüller, Hanns
dbc374ba-28c4-43ef-a459-b131cf865894
Chinnery, Patrick F
87789d1a-5265-4815-9f11-194ed9b4ad94
Klopstock, Thomas
6f505e28-e765-4076-8ed2-48e67320f44f
Horvath, Rita
e41c9ffa-b0a0-4ebb-a44a-b98a2c6c23cd

Walter, Maggie C, Czermin, Birgit, Muller-Ziermann, Solvig, Bulst, Stefanie, Stewart, Joanna D, Hudson, Gavin, Schneiderat, Peter, Abicht, Angela, Holinski-Feder, Elke, Lochmüller, Hanns, Chinnery, Patrick F, Klopstock, Thomas and Horvath, Rita (2010) Late-onset ptosis and myopathy in a patient with a heterozygous insertion in POLG2. Journal of Neurology, 257 (9), 1517-1523. (doi:10.1007/s00415-010-5565-9). (PMID:20405137)

Record type: Article

Abstract

Polymerase gamma 1 (POLG) mutations are a frequent cause of both autosomal dominant and recessive complex neurological phenotypes. In contrast, only a single pathogenic mutation in one patient was reported in POLG2 so far. Here we describe a 62-year-old woman, carrying a novel heterozygous sequence variant in the POLG2 gene. She developed bilateral ptosis at 30 years of age, followed by exercise intolerance, muscle weakness and mild CK increase in her late forties. Muscle histology and respiratory chain activities were normal. Southern blot and long range PCR detected multiple mtDNA deletions, but no depletion in muscle DNA. Sequencing of POLG, PEO1, ANT1, OPA1 and RRM2B showed normal results. A novel heteroallelic 24 bp insertion (c.1207_1208ins24) was detected in POLG2. This 24 bp insertion into exon 7 causes missplicing and loss of exon 7 in myoblast cDNA. We did not detect POLG2 mutations in 62 patients with multiple mtDNA deletions in muscle DNA, suggesting that POLG2 mutations may represent a rare cause of autosomal dominant PEO.

Text
Walter et al, 2010.pdf - Other
Restricted to Repository staff only
Request a copy

More information

Published date: September 2010
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 355909
URI: http://eprints.soton.ac.uk/id/eprint/355909
ISSN: 0340-5354
PURE UUID: 5e0f8c3c-0b82-4d4c-99ec-c04075921595
ORCID for Joanna D Stewart: ORCID iD orcid.org/0000-0002-2608-1967

Catalogue record

Date deposited: 04 Sep 2013 16:51
Last modified: 18 Feb 2021 17:20

Export record

Altmetrics

Contributors

Author: Maggie C Walter
Author: Birgit Czermin
Author: Solvig Muller-Ziermann
Author: Stefanie Bulst
Author: Joanna D Stewart ORCID iD
Author: Gavin Hudson
Author: Peter Schneiderat
Author: Angela Abicht
Author: Elke Holinski-Feder
Author: Hanns Lochmüller
Author: Patrick F Chinnery
Author: Thomas Klopstock
Author: Rita Horvath

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×