Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis

Bradley N Smith; Simon D Topp; Claudia Fallini; Hideki Shibata; Han-Jou Chen; Claire Troakes; Andrew King; Nicola Ticozzi; Kevin P Kenna; Athina Soragia-Gkazi; Jack W Miller; Akane Sato; Diana Marques Dias; Maryangel Jeon; Caroline Vance; Chun Hao Wong; Martina de Majo; Wejdan Kattuah; Jacqueline C Mitchell; Emma L Scotter; Nicholas W Parkin; Peter C Sapp; Matthew Nolan; Peter J Nestor; Michael Simpson; Michael Weale; Monkel Lek; Frank Baas; J M Vianney de Jong; Anneloor L M A Ten Asbroek; Alberto Garcia Redondo; Jesús Esteban-Pérez; Cinzia Tiloca; Federico Verde; Stefano Duga; Nigel Leigh; Hardev Pall; Karen E Morrison; Ammar Al-Chalabi; Pamela J Shaw; Janine Kirby; Martin R Turner; Kevin Talbot; Orla Hardiman; Jonathan D Glass; Jacqueline De Belleroche; Masatoshi Maki; Stephen E Moss; Christopher Miller; Cinzia Gellera; Antonia Ratti; Safa Al-Sarraj; Robert H Brown; Vincenzo Silani; John E Landers; Christopher E Shaw

doi:10.1126/scitranslmed.aad9157

Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis

Bradley N Smith, Simon D Topp, Claudia Fallini, Hideki Shibata, Han-Jou Chen, Claire Troakes, Andrew King, Nicola Ticozzi, Kevin P Kenna, Athina Soragia-Gkazi, Jack W Miller, Akane Sato, Diana Marques Dias, Maryangel Jeon, Caroline Vance, Chun Hao Wong, Martina de Majo, Wejdan Kattuah, Jacqueline C Mitchell, Emma L ScotterNicholas W Parkin, Peter C Sapp, Matthew Nolan, Peter J Nestor, Michael Simpson, Michael Weale, Monkel Lek, Frank Baas, J M Vianney de Jong, Anneloor L M A Ten Asbroek, Alberto Garcia Redondo, Jesús Esteban-Pérez, Cinzia Tiloca, Federico Verde, Stefano Duga, Nigel Leigh, Hardev Pall, Karen E Morrison, Ammar Al-Chalabi, Pamela J Shaw, Janine Kirby, Martin R Turner, Kevin Talbot, Orla Hardiman, Jonathan D Glass, Jacqueline De Belleroche, Masatoshi Maki, Stephen E Moss, Christopher Miller, Cinzia Gellera, Antonia Ratti, Safa Al-Sarraj, Robert H Brown, Vincenzo Silani, John E Landers, Christopher E Shaw

Research output: Contribution to journal › Article › peer-review

88 Citations (Scopus)

433 Downloads (Pure)

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. We screened 751 familial ALS patient whole-exome sequences and identified six mutations including p.D40G in the ANXA11 gene in 13 individuals. The p.D40G mutation was absent from 70,000 control whole-exome sequences. This mutation segregated with disease in two kindreds and was present in another two unrelated cases (P = 0.0102), and all mutation carriers shared a common founder haplotype. Annexin A11-positive protein aggregates were abundant in spinal cord motor neurons and hippocampal neuronal axons in an ALS patient carrying the p.D40G mutation. Transfected human embryonic kidney cells expressing ANXA11 with the p.D40G mutation and other N-terminal mutations showed altered binding to calcyclin, and the p.R235Q mutant protein formed insoluble aggregates. We conclude that mutations in ANXA11 are associated with ALS and implicate defective intracellular protein trafficking in disease pathogenesis.

Original language	English
Article number	eaad9157
Number of pages	16
Journal	Science Translational Medicine
Volume	9
Issue number	388
Early online date	3 May 2017
DOIs	https://doi.org/10.1126/scitranslmed.aad9157
Publication status	Published - 3 May 2017

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1126/scitranslmed.aad9157

Mutations in the vesicular_SMITH_Accepted4January2017_GREEN AAMAccepted author manuscript, 5.87 MB

Cite this

Smith, B. N., Topp, S. D., Fallini, C., Shibata, H., Chen, H-J., Troakes, C., King, A., Ticozzi, N., Kenna, K. P., Soragia-Gkazi, A., Miller, J. W., Sato, A., Dias, D. M., Jeon, M., Vance, C., Wong, C. H., de Majo, M., Kattuah, W., Mitchell, J. C., ... Shaw, C. E. (2017). Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis. Science Translational Medicine, 9(388), [eaad9157]. https://doi.org/10.1126/scitranslmed.aad9157

@article{144e6614fd054319b73183fc430c7e2e,

title = "Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis",

abstract = "Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. We screened 751 familial ALS patient whole-exome sequences and identified six mutations including p.D40G in the ANXA11 gene in 13 individuals. The p.D40G mutation was absent from 70,000 control whole-exome sequences. This mutation segregated with disease in two kindreds and was present in another two unrelated cases (P = 0.0102), and all mutation carriers shared a common founder haplotype. Annexin A11-positive protein aggregates were abundant in spinal cord motor neurons and hippocampal neuronal axons in an ALS patient carrying the p.D40G mutation. Transfected human embryonic kidney cells expressing ANXA11 with the p.D40G mutation and other N-terminal mutations showed altered binding to calcyclin, and the p.R235Q mutant protein formed insoluble aggregates. We conclude that mutations in ANXA11 are associated with ALS and implicate defective intracellular protein trafficking in disease pathogenesis.",

author = "Smith, {Bradley N} and Topp, {Simon D} and Claudia Fallini and Hideki Shibata and Han-Jou Chen and Claire Troakes and Andrew King and Nicola Ticozzi and Kenna, {Kevin P} and Athina Soragia-Gkazi and Miller, {Jack W} and Akane Sato and Dias, {Diana Marques} and Maryangel Jeon and Caroline Vance and Wong, {Chun Hao} and {de Majo}, Martina and Wejdan Kattuah and Mitchell, {Jacqueline C} and Scotter, {Emma L} and Parkin, {Nicholas W} and Sapp, {Peter C} and Matthew Nolan and Nestor, {Peter J} and Michael Simpson and Michael Weale and Monkel Lek and Frank Baas and {Vianney de Jong}, {J M} and {Ten Asbroek}, {Anneloor L M A} and Redondo, {Alberto Garcia} and Jes{\'u}s Esteban-P{\'e}rez and Cinzia Tiloca and Federico Verde and Stefano Duga and Nigel Leigh and Hardev Pall and Morrison, {Karen E} and Ammar Al-Chalabi and Shaw, {Pamela J} and Janine Kirby and Turner, {Martin R} and Kevin Talbot and Orla Hardiman and Glass, {Jonathan D} and {De Belleroche}, Jacqueline and Masatoshi Maki and Moss, {Stephen E} and Christopher Miller and Cinzia Gellera and Antonia Ratti and Safa Al-Sarraj and Brown, {Robert H} and Vincenzo Silani and Landers, {John E} and Shaw, {Christopher E}",

note = "Copyright {\textcopyright} 2017, American Association for the Advancement of Science.",

year = "2017",

month = may,

day = "3",

doi = "10.1126/scitranslmed.aad9157",

language = "English",

volume = "9",

journal = "Science Translational Medicine",

issn = "1946-6234",

publisher = "American Association for the Advancement of Science",

number = "388",

}

Smith, BN , Topp, SD, Fallini, C, Shibata, H, Chen, H-J , Troakes, C, King, A, Ticozzi, N, Kenna, KP, Soragia-Gkazi, A , Miller, JW, Sato, A, Dias, DM, Jeon, M, Vance, C , Wong, CH , de Majo, M , Kattuah, W , Mitchell, JC, Scotter, EL, Parkin, NW, Sapp, PC, Nolan, M, Nestor, PJ, Simpson, M , Weale, M, Lek, M, Baas, F, Vianney de Jong, JM, Ten Asbroek, ALMA, Redondo, AG, Esteban-Pérez, J, Tiloca, C, Verde, F, Duga, S, Leigh, N, Pall, H, Morrison, KE, Al-Chalabi, A, Shaw, PJ, Kirby, J, Turner, MR, Talbot, K, Hardiman, O, Glass, JD, De Belleroche, J, Maki, M, Moss, SE, Miller, C, Gellera, C, Ratti, A, Al-Sarraj, S, Brown, RH, Silani, V, Landers, JE & Shaw, CE 2017, 'Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis', Science Translational Medicine, vol. 9, no. 388, eaad9157. https://doi.org/10.1126/scitranslmed.aad9157

TY - JOUR

T1 - Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis

AU - Smith, Bradley N

AU - Topp, Simon D

AU - Fallini, Claudia

AU - Shibata, Hideki

AU - Chen, Han-Jou

AU - Troakes, Claire

AU - King, Andrew

AU - Ticozzi, Nicola

AU - Kenna, Kevin P

AU - Soragia-Gkazi, Athina

AU - Miller, Jack W

AU - Sato, Akane

AU - Dias, Diana Marques

AU - Jeon, Maryangel

AU - Vance, Caroline

AU - Wong, Chun Hao

AU - de Majo, Martina

AU - Kattuah, Wejdan

AU - Mitchell, Jacqueline C

AU - Scotter, Emma L

AU - Parkin, Nicholas W

AU - Sapp, Peter C

AU - Nolan, Matthew

AU - Nestor, Peter J

AU - Simpson, Michael

AU - Weale, Michael

AU - Lek, Monkel

AU - Baas, Frank

AU - Vianney de Jong, J M

AU - Ten Asbroek, Anneloor L M A

AU - Redondo, Alberto Garcia

AU - Esteban-Pérez, Jesús

AU - Tiloca, Cinzia

AU - Verde, Federico

AU - Duga, Stefano

AU - Leigh, Nigel

AU - Pall, Hardev

AU - Morrison, Karen E

AU - Al-Chalabi, Ammar

AU - Shaw, Pamela J

AU - Kirby, Janine

AU - Turner, Martin R

AU - Talbot, Kevin

AU - Hardiman, Orla

AU - Glass, Jonathan D

AU - De Belleroche, Jacqueline

AU - Maki, Masatoshi

AU - Moss, Stephen E

AU - Miller, Christopher

AU - Gellera, Cinzia

AU - Ratti, Antonia

AU - Al-Sarraj, Safa

AU - Brown, Robert H

AU - Silani, Vincenzo

AU - Landers, John E

AU - Shaw, Christopher E

PY - 2017/5/3

Y1 - 2017/5/3

N2 - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. We screened 751 familial ALS patient whole-exome sequences and identified six mutations including p.D40G in the ANXA11 gene in 13 individuals. The p.D40G mutation was absent from 70,000 control whole-exome sequences. This mutation segregated with disease in two kindreds and was present in another two unrelated cases (P = 0.0102), and all mutation carriers shared a common founder haplotype. Annexin A11-positive protein aggregates were abundant in spinal cord motor neurons and hippocampal neuronal axons in an ALS patient carrying the p.D40G mutation. Transfected human embryonic kidney cells expressing ANXA11 with the p.D40G mutation and other N-terminal mutations showed altered binding to calcyclin, and the p.R235Q mutant protein formed insoluble aggregates. We conclude that mutations in ANXA11 are associated with ALS and implicate defective intracellular protein trafficking in disease pathogenesis.

AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. We screened 751 familial ALS patient whole-exome sequences and identified six mutations including p.D40G in the ANXA11 gene in 13 individuals. The p.D40G mutation was absent from 70,000 control whole-exome sequences. This mutation segregated with disease in two kindreds and was present in another two unrelated cases (P = 0.0102), and all mutation carriers shared a common founder haplotype. Annexin A11-positive protein aggregates were abundant in spinal cord motor neurons and hippocampal neuronal axons in an ALS patient carrying the p.D40G mutation. Transfected human embryonic kidney cells expressing ANXA11 with the p.D40G mutation and other N-terminal mutations showed altered binding to calcyclin, and the p.R235Q mutant protein formed insoluble aggregates. We conclude that mutations in ANXA11 are associated with ALS and implicate defective intracellular protein trafficking in disease pathogenesis.

UR - http://www.scopus.com/inward/record.url?scp=85019253263&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aad9157

DO - 10.1126/scitranslmed.aad9157

M3 - Article

C2 - 28469040

SN - 1946-6234

VL - 9

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 388

M1 - eaad9157

ER -

Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this