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Journal articles
A diagnostic flow chart for POLG-related diseases based on signs sensitivity and specificity.
Maya Tchikviladzé
1, 2
Mylène Gilleron
3, 4, 5
Thierry Maisonobe
1
Damien Galanaud
6
Pascal Laforêt
1
Alexandra Durr
5, 7, 1
Bruno Eymard
5, 1, 7
Fanny Mochel
7, 1
Hélène Ogier
8
Anthony Béhin
1
Tanya Stojkovic
1
Bertrand Degos
1
Isabelle Gourfinkel-An
1
Frederic Sedel
7, 1
Mathieu Anheim
1
Alexis Elbaz
9
Karine Viala
1
Marie Vidailhet
1, 7
Alexis Brice
5, 7, 1
Claude Jardel
3, 4
Anne Lombès
3, 4, *
*
Corresponding author
5
ARAMIS - Algorithms, models and methods for images and signals of the human brain
Inria Paris-Rocquencourt, UPMC - Université Pierre et Marie Curie - Paris 6, ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
Maya Tchikviladzé 1, 2
Author
Mylène Gilleron 3, 4, 5
Author
Thierry Maisonobe 1
Author
Damien Galanaud 6
Author
Pascal Laforêt 1
Author
Alexandra Durr 5, 7, 1
Author
Bruno Eymard 5, 1, 7
Author
Fanny Mochel 7, 1
Author
Isabelle Gourfinkel-An 1
Author
Frederic Sedel 7, 1
Author
Mathieu Anheim 1
Author
Alexis Elbaz 9
Author
Karine Viala 1
Author
Marie Vidailhet 1, 7
Author
Alexis Brice 5, 7, 1
Author
Claude Jardel 3, 4
Author
Anne Lombès 3, 4
Correspondent author
1
CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
- Sorbonne Université (France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
2
CIC AP-HP (pitie-Salpetriere)/inserm (Gh Pitie-Salpetriere PARIS VI 47, Boulevard de L'Hopital 75651 PARIS CEDEX 13 - France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : CIC9503 (101, rue de Tolbiac, 75013 Paris - France)
3
IC UM3 (UMR 8104 / U1016) - Institut Cochin (22 rue Méchain, 75014 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1016 (101, rue de Tolbiac, 75013 Paris - France)
- UPD5 - Université Paris Descartes - Paris 5 : UM 3 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR 8104 (France)
4
Service de Biochimie Métabolique [CHU Pitié-Salpêtrière] (France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
- Sorbonne Université (France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
5
ARAMIS - Algorithms, models and methods for images and signals of the human brain (Hôpital de la Pitié-Salpêtrière Batiment ICM 47 boulevard de l'hopital 75013 Paris - France)
- Inria Paris-Rocquencourt (INRIA Rocquencourt : Domaine de Voluceau, Rocquencourt B.P. 105 78153 le Chesnay Cedex - France)
- Inria - Institut National de Recherche en Informatique et en Automatique (Domaine de Voluceau Rocquencourt - BP 105 78153 Le Chesnay Cedex - France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
- ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (47-83 Boulevard de l'Hôpital 75651 Paris Cedex 13 - France)
- UPMC - Université Pierre et Marie Curie - Paris 6 : UM75 (4 place Jussieu - 75005 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1127 (101, rue de Tolbiac, 75013 Paris - France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
- Sorbonne Université (France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CNRS - Centre National de la Recherche Scientifique : UMR7225 (France)
6
Service de Neuroradiologie [CHU Pitié-Salpêtrière] (France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
- Sorbonne Université (France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
7
CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (GH Pitié-Salpêtrière 47, boulevard de l'Hôpital 75651 Paris cedex 13 - France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U975 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7225 (France)
8
Hôpital Robert Debré (Reims - France)
- Hôpital Robert Debré (France)
- CHU Reims - Centre Hospitalier Universitaire de Reims (45, rue Cognacq-Jay 51100 Reims - France)
9
CESP - Centre de recherche en épidémiologie et santé des populations (16 avenue Paul Vaillant Couturier 94807 Villejuif Cedex, France - France)
- UVSQ - Université de Versailles Saint-Quentin-en-Yvelines : UMR U1018 (55 avenue de Paris - 78035 Versailles cedex - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1018 (101, rue de Tolbiac, 75013 Paris - France)
- UP11 - Université Paris-Sud - Paris 11 (Bâtiment 300 - 91405 Orsay cedex - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- Hôpital Paul Brousse (12 Avenue Paul Vaillant Couturier, 94800 Villejuif - France)
Abstract : OBJECTIVE: Diseases due to mutations of POLG gene, encoding the mitochondrial DNA polymerase, are reputed to have very diverse clinical presentations and have been proposed to cause up to 25% adult mitochondrial diseases. Our objective was the evaluation of the specificity and sensitivity of the signs encountered with POLG mutations. DESIGN: Forty-four patients out of 154 with sequenced POLG gene had mutations affecting either one (POLG(+/-) group) or two POLG alleles (POLG(+/+) group). Phenotyping included clinical signs, electroneuromyography and brain imaging while mitochondrial investigations encompassed muscle histochemistry, respiratory chain assays and search for multiple mitochondrial deletions. The specificity and sensitivity of the signs associated with POLG mutations were analysed by comparison between POLG(+/+) and patients without POLG mutation. RESULTS: High sensitivity but low specificity was observed with single signs such as axonal sensory neuropathy, cerebellar syndrome, movement disorders and weakness involving ocular, pharyngeal, axial and/or limb muscles. Specificity was increased with combination of previous signs plus psychiatric symptoms, cognitive impairment and epilepsy. High specificity and sensitivity was only obtained with sensory neuronopathy associated with one of the following signs: weakness of ocular, pharyngeal, axial and/or limb muscles. Mitochondrial investigations did not suffice for diagnosis. The widespread neuromuscular signs were often present since disease onset and were the rule above 50 years of age leading to a very low probability of POLG mutations in patients with less than three signs and absent sensory neuropathy. CONCLUSIONS: Phenotypes associated with POLG mutations follow a reproducible pattern, which allows establishing a diagnostic flow chart.
Document type :
Journal articles
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https://www.hal.inserm.fr/inserm-01067950
Contributor : Mireille Bos <>
Submitted on : Wednesday, September 24, 2014 - 2:00:12 PM
Last modification on : Monday, March 29, 2021 - 2:41:13 PM
Long-term archiving on: : Friday, April 14, 2017 - 11:45:39 AM
Contributor : Mireille Bos <>
Submitted on : Wednesday, September 24, 2014 - 2:00:12 PM
Last modification on : Monday, March 29, 2021 - 2:41:13 PM
Long-term archiving on: : Friday, April 14, 2017 - 11:45:39 AM
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Identifiers
- HAL Id : inserm-01067950, version 1
- DOI : 10.1136/jnnp-2013-306799
- PUBMED : 25118206
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INSERM | UNIV-PARIS5 | CNRS | INRIA | UPMC | ICM | ARAMISLAB | ARAMILAB | USPC | CESP | UVSQ | SORBONNE-UNIVERSITE | SU-MEDECINE | UNIV-PARIS | UP-SANTE | SU-TI
Citation
Maya Tchikviladzé, Mylène Gilleron, Thierry Maisonobe, Damien Galanaud, Pascal Laforêt, et al.. A diagnostic flow chart for POLG-related diseases based on signs sensitivity and specificity.. Journal of Neurology, Neurosurgery and Psychiatry, BMJ Publishing Group, 2015, 86 (6), pp.646-54. ⟨10.1136/jnnp-2013-306799⟩. ⟨inserm-01067950⟩
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