Journal articles
Mutations in BCAP31 Cause a Severe X-Linked Phenotype with Deafness, Dystonia, and Central Hypomyelination and Disorganize the Golgi Apparatus
Pierre Cacciagli
1
Julie Sutera-Sardo
1
Ana Borges-Correia
1
Jean-Christophe Roux
1
Imen Dorboz
2
Jean-Pierre Desvignes
1
Catherine Badens
3, 1, 4
Marc Délépine
5
Mark Lathrop
6
Pierre Cau
1
Nicolas Lévy
1, 4
Nadine Girard
7
Pierre Sarda
8
Odile Boespflug-Tanguy
9
Laurent Villard
1, *
*
Corresponding author
Pierre Cacciagli 1
Author
Julie Sutera-Sardo 1
Author
Ana Borges-Correia 1
Author
Jean-Christophe Roux 1
Author IdHAL : jc-roux ResearcherId : http://www.researcherid.com/rid/S-2563-2016 ORCID : https://orcid.org/0000-0002-9721-8844
Imen Dorboz 2
Author
Jean-Pierre Desvignes 1
Author IdHAL : jean-pierre-desvignes ResearcherId : http://www.researcherid.com/rid/I-2858-2016 ORCID : https://orcid.org/0000-0003-3142-1994
Catherine Badens 3, 1, 4
Author IdHAL : catherine-badens ORCID : https://orcid.org/0000-0001-9024-310X
Marc Délépine 5
Author
Mark Lathrop 6
Author
Pierre Cau 1
Author
Nicolas Lévy 1, 4
Author IdHAL : nicolas-levy
Nadine Girard 7
Author
Pierre Sarda 8
Author
Odile Boespflug-Tanguy 9
Author
Laurent Villard 1
Correspondent author IdHAL : laurent-villard ResearcherId : http://www.researcherid.com/rid/E-3941-2016 ORCID : https://orcid.org/0000-0001-6657-5008
1
GMGF - Génétique Médicale et Génomique Fonctionnelle (Faculté de Médecine - 27 boulevard Jean Moulin 13385 Marseille Cedex 05 - France)
- AMU - Aix Marseille Université : U910 (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
- APHM - Assistance Publique - Hôpitaux de Marseille (Direction générale AP-HM 80, rue Brochier 13 354 Marseille Cedex 5 - France)
- TIMONE - Hôpital de la Timone [CHU - APHM] (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U910 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : U910 (France)
2
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)
- AP-HP - 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)
3
Centre de référence maladie rare Thalassémie (Hôpital d'enfants de la Timone, Rue Saint-Pierre, Marseille - France)
- APHM - Assistance Publique - Hôpitaux de Marseille (Direction générale AP-HM 80, rue Brochier 13 354 Marseille Cedex 5 - France)
- TIMONE - Hôpital de la Timone [CHU - APHM] (France)
4
Département de génétique médicale [Hôpital de la Timone - APHM] (Hôpital de la Timone
264, rue Saint Pierre 13385 Marseille Cedex 5 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U491 (101, rue de Tolbiac, 75013 Paris - France)
- TIMONE - Hôpital de la Timone [CHU - APHM] (France)
- APHM - Assistance Publique - Hôpitaux de Marseille (Direction générale AP-HM 80, rue Brochier 13 354 Marseille Cedex 5 - France)
- AMU - Aix Marseille Université (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
5
CEA - Commissariat à l'énergie atomique et aux énergies alternatives (Centre de Saclay
Centre de Grenoble
Centre de Cadarache
etc - France)
6
CNG - Centre National de Génotypage (Centre National de Génotypage 2 rue Gaston Crémieux CP5721 91057 EVRY Cedex - France)
- CEA - Commissariat à l'énergie atomique et aux énergies alternatives : DSV/IG (Centre de Saclay Centre de Grenoble Centre de Cadarache etc - France)
7
TIMONE - Hôpital de la Timone [CHU - APHM] (France)
8
CHU de Montpellier (France)
- CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier] (191 avenue du doyen Gaston Giraud 34295 Montpellier cedex 5 - France)
9
GReD - Génétique, Reproduction et Développement - Clermont Auvergne (France)
- CNRS - Centre National de la Recherche Scientifique : UMR6293 (France)
- UCA - Université Clermont Auvergne (49, bd François-Mitterrand / CS 60032 / 63001 Clermont-Ferrand Cedex 1 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1103 (101, rue de Tolbiac, 75013 Paris - France)
Abstract : BAP31 is one of the most abundant endoplasmic reticulum (ER) membrane proteins. It is a chaperone protein involved in several pathways , including ER-associated degradation, export of ER proteins to the Golgi apparatus, and programmed cell death. BAP31 is encoded by BCAP31, located in human Xq28 and highly expressed in neurons. We identified loss-of-function mutations in BCAP31 in seven individuals from three families. These persons suffered from motor and intellectual disabilities, dystonia, sensorineural deafness, and white-matter changes, which together define an X-linked syndrome. In the primary fibroblasts of affected individuals, we found that BCAP31 deficiency altered ER morphology and caused a disorganization of the Golgi apparatus in a significant proportion of cells. Contrary to what has been described with transient-RNA-interference experiments, we demonstrate that constitutive BCAP31 deficiency does not activate the unfolded protein response or cell-death effectors. Rather, our data demonstrate that the lack of BAP31 disturbs ER metabolism and impacts the Golgi apparatus, highlighting an important role for BAP31 in ER-to-Golgi crosstalk. These findings provide a molecular basis for a Mendelian syndrome and link intracellular protein trafficking to severe congenital brain dysfunction and deafness.
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Journal articles
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https://hal-amu.archives-ouvertes.fr/hal-01668665
Contributor : Laurent Villard <>
Submitted on : Friday, March 23, 2018 - 4:52:06 PM
Last modification on : Monday, December 14, 2020 - 3:40:08 PM
Long-term archiving on: : Tuesday, September 11, 2018 - 9:28:25 AM
Contributor : Laurent Villard <>
Submitted on : Friday, March 23, 2018 - 4:52:06 PM
Last modification on : Monday, December 14, 2020 - 3:40:08 PM
Long-term archiving on: : Tuesday, September 11, 2018 - 9:28:25 AM
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- HAL Id : hal-01668665, version 1
- DOI : 10.1016/j.ajhg.2013.07.023
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UNIV-AMU | USPC | JACOB | GRED | CEA-DRF | CNRS | PRES_CLERMONT | UNIV-PARIS7 | CEA | MMG | ACL-SVSAE | PHARMA-AMU | UNIV-PARIS
Citation
Pierre Cacciagli, Julie Sutera-Sardo, Ana Borges-Correia, Jean-Christophe Roux, Imen Dorboz, et al.. Mutations in BCAP31 Cause a Severe X-Linked Phenotype with Deafness, Dystonia, and Central Hypomyelination and Disorganize the Golgi Apparatus. American Journal of Human Genetics, Elsevier (Cell Press), 2013, 93, pp.579-586. ⟨10.1016/j.ajhg.2013.07.023⟩. ⟨hal-01668665⟩
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