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Journal articles
Insertion of an extra copy of Xq22.2 into 1p36 results in functional duplication of the PLP1 gene in a girl with classical Pelizaeus-Merzbacher disease
Julien Masliah-Planchon
1
Céline Dupont
2
George Vartzelis
3
Aurélien Trimouille
1
Eléonore Eymard-Pierre
4, 5
Mathilde Gay-Bellile
4, 5
Florence Renaldo
6, 1
Imen Dorboz
1
Cécile Pagan
1
Samuel Quentin
7
Monique Elmaleh
8
Christina Kotsogianni
3
Elissavet Konstantelou
3
Séverine Drunat
1
Anne-Claude Tabet
2
Odile Boespflug-Tanguy
1, 6, *
*
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Julien Masliah-Planchon 1
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Céline Dupont 2
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George Vartzelis 3
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Aurélien Trimouille 1
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Eléonore Eymard-Pierre 4, 5
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Mathilde Gay-Bellile 4, 5
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Florence Renaldo 6, 1
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Imen Dorboz 1
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Cécile Pagan 1
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Samuel Quentin 7
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Monique Elmaleh 8
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Christina Kotsogianni 3
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Elissavet Konstantelou 3
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Séverine Drunat 1
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Anne-Claude Tabet 2
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Odile Boespflug-Tanguy 1, 6
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1
PROTECT - Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (Hôpital Robert Debré - Bâtiment Ecran/3ème étage Point Jaune - 48 Bd Serurier 75019 Paris - France)
- APHP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- Hôpital Robert Debré (France)
- UPD7 - Université Paris Diderot - Paris 7 (5 rue Thomas-Mann - 75205 Paris cedex 13 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1141 (101, rue de Tolbiac, 75013 Paris - France)
2
UF de Cytogénétique (48 Bd Sérurier, 75019 Paris - France)
- AP-HP Hôpital universitaire Robert-Debré [Paris] ( 48, boulevard Sérurier – 75019 Paris - France)
3
Paediatric Neurology (Athens - Greece)
- "A. & P. Kyriakou" Children's Hospital Athens (Athens - Greece)
4
ERTICa - Equipe de recherche sur les traitements individualisés des cancers (Centre Jean Perrin Service d'Anatomopathologie 58, rue Montalembert 63011 Clermont-Ferrand Faculté de Médecine Rez de chaussée R3 & CBRV 28 place Henri-Dunant 63000 Clermont-Ferrand - France)
- UdA - Université d'Auvergne - Clermont-Ferrand I : EA4677 (49, Boulevard François-Mitterrand / CS 60032 / 63001 Clermont-Ferrand Cedex 1 - France)
5
Cytogénétique Médicale (Clermont-Ferrand - France)
- CHU Clermont-Ferrand (France)
- UdA - Université d'Auvergne - Clermont-Ferrand I (49, Boulevard François-Mitterrand / CS 60032 / 63001 Clermont-Ferrand Cedex 1 - France)
- Hôpital d'Estaing (France)
6
Service de neurologie pédiatrique et maladies métaboliques (48, boulevard Sérurier 75935 PARIS CEDEX 19 - France)
- APHP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- Hôpital Robert Debré (France)
- UPD7 - Université Paris Diderot - Paris 7 (5 rue Thomas-Mann - 75205 Paris cedex 13 - France)
7
IUH - Institut Universitaire d'Hématologie (Université Paris Diderot, 1 Av. Claude Vellefaux 75010 Paris - France)
- UPD7 - Université Paris Diderot - Paris 7 (5 rue Thomas-Mann - 75205 Paris cedex 13 - France)
8
Service d'imagerie pédiatrique (48 Boulevard Sérurier 75935 Paris - France)
- APHP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- Hôpital Robert Debré (France)
- UPD7 - Université Paris Diderot - Paris 7 (5 rue Thomas-Mann - 75205 Paris cedex 13 - France)
Abstract : AbstractBackgroundPelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder characterized by nystagmus, hypotonia, ataxia, progressive spasticity, and cognitive decline. PMD classically results from a duplication of a genomic segment encompassing the entire PLP1 gene. Since the PLP1 gene is located in Xq22, PMD affects mostly boys.Methods and resultsHere we report the case of a girl with typical PMD. Copy number analysis of the PLP1 locus revealed a duplication of the entire gene and FISH analysis showed that the extra copy of the PLP1 gene was actually inserted in chromosome 1p36. This insertion of an additional copy of PLP1 in an autosome led to a functional duplication irrespective of the X-inactivation pattern. Subsequent overexpression of PLP1 was the cause of the PMD phenotype observed in this girl. Further sequencing of the breakpoint junction revealed a microhomology and thus suggested a replication based mechanism (such as FoSTeS or MMBIR).ConclusionThis case emphasizes the susceptibility of the PLP1 locus to complex rearrangement likely driven by the Xq22 local genomic architecture. In addition, careful consideration should be given to girls with classical PMD clinical features since they usually experience complex PLP1 genomic alteration with a distinct risk of inheritance.
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Journal articles
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https://www.hal.inserm.fr/inserm-01264503
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Submitted on : Friday, January 29, 2016 - 12:43:22 PM
Last modification on : Friday, March 27, 2020 - 3:04:18 AM
Document(s) archivé(s) le : Friday, November 11, 2016 - 8:06:35 PM
Contributor : Bmc Bmc <>
Submitted on : Friday, January 29, 2016 - 12:43:22 PM
Last modification on : Friday, March 27, 2020 - 3:04:18 AM
Document(s) archivé(s) le : Friday, November 11, 2016 - 8:06:35 PM
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12881_2015_Article_226.pdf
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- HAL Id : inserm-01264503, version 1
- DOI : 10.1186/s12881-015-0226-6
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UNIV-PARIS7 | ACL-SVSAE | USPC | PRES_CLERMONT | IMOST
Citation
Julien Masliah-Planchon, Céline Dupont, George Vartzelis, Aurélien Trimouille, Eléonore Eymard-Pierre, et al.. Insertion of an extra copy of Xq22.2 into 1p36 results in functional duplication of the PLP1 gene in a girl with classical Pelizaeus-Merzbacher disease. BMC Medical Genetics, BioMed Central, 2015, 16 (1), pp.77. ⟨10.1186/s12881-015-0226-6⟩. ⟨inserm-01264503⟩
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