VAMP1 mutation causes dominant hereditary spastic ataxia in newfoundland families

Cynthia V. Bourassa; Inge A. Meijer; Nancy D. Merner; Kanwal K. Grewal; Mark G. Stefanelli; Kathleen Hodgkinson; Elizabeth J. Ives; William Pryse-Phillips; Mandar Jog; Kym Boycott; David A. Grimes; Sharan Goobie; Richard Leckey; Patrick A. Dion; Guy A. Rouleau

doi:10.1016/j.ajhg.2012.07.018

VAMP1 mutation causes dominant hereditary spastic ataxia in newfoundland families

Cynthia V. Bourassa, Inge A. Meijer, Nancy D. Merner, Kanwal K. Grewal, Mark G. Stefanelli, Kathleen Hodgkinson, Elizabeth J. Ives, William Pryse-Phillips, Mandar Jog, Kym Boycott, David A. Grimes, Sharan Goobie, Richard Leckey, Patrick A. Dion, Guy A. Rouleau

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

40 Citations (Scopus)

Abstract

Our group previously described and mapped to chromosomal region 12p13 a form of dominantly inherited hereditary spastic ataxia (HSA) in three large Newfoundland (Canada) families. This report identifies vesicle-associated membrane protein 1 (VAMP1), which encodes a critical protein for synaptic exocytosis, as the responsible gene. In total, 50 affected individuals from these families and three independent probands from Ontario (Canada) share the disease phenotype together with a disruptive VAMP1 mutation that affects a critical donor site for the splicing of VAMP1 isoforms. This mutation leads to the loss of the only VAMP1 isoform (VAMP1A) expressed in the nervous system, thus highlighting an association between the well-studied VAMP1 and a neurological disorder. Given the variable phenotype seen in the affected individuals examined here, we believe that VAMP1 should be tested for mutations in patients with either ataxia or spastic paraplegia.

Original language	English
Pages (from-to)	548-552
Number of pages	5
Journal	American Journal of Human Genetics
Volume	91
Issue number	3
DOIs	https://doi.org/10.1016/j.ajhg.2012.07.018
Publication status	Published - Sept 7 2012
Externally published	Yes

Bibliographical note

Funding Information:
The authors would like to thank the family members and the volunteer controls, as well as Roger Green for kindly providing the latter ones. We also thank Weichun Lin for information about the heterozygous mouse. Special thanks to Loubna Jouan and Anna Szuto for their technical assistance. C.V.B. is supported by the Canadian Institutes for Health Research through the Master’s Award: Frederick Banting and Charles Best Canada Graduate Scholarships. G.A.R. holds the Canada Research Chair and a Jeanne et J. Louis Levesque Chair for the Genetics of Brain Diseases.

ASJC Scopus Subject Areas

Genetics
Genetics(clinical)

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

Access to Document

10.1016/j.ajhg.2012.07.018

Cite this

Bourassa, C. V., Meijer, I. A., Merner, N. D., Grewal, K. K., Stefanelli, M. G., Hodgkinson, K., Ives, E. J., Pryse-Phillips, W., Jog, M., Boycott, K., Grimes, D. A., Goobie, S., Leckey, R., Dion, P. A., & Rouleau, G. A. (2012). VAMP1 mutation causes dominant hereditary spastic ataxia in newfoundland families. American Journal of Human Genetics, 91(3), 548-552. https://doi.org/10.1016/j.ajhg.2012.07.018

Bourassa, CV, Meijer, IA, Merner, ND, Grewal, KK, Stefanelli, MG, Hodgkinson, K, Ives, EJ, Pryse-Phillips, W, Jog, M, Boycott, K, Grimes, DA, Goobie, S, Leckey, R, Dion, PA & Rouleau, GA 2012, 'VAMP1 mutation causes dominant hereditary spastic ataxia in newfoundland families', American Journal of Human Genetics, vol. 91, no. 3, pp. 548-552. https://doi.org/10.1016/j.ajhg.2012.07.018

@article{04cca01797384df0b823955c35c723b0,

title = "VAMP1 mutation causes dominant hereditary spastic ataxia in newfoundland families",

abstract = "Our group previously described and mapped to chromosomal region 12p13 a form of dominantly inherited hereditary spastic ataxia (HSA) in three large Newfoundland (Canada) families. This report identifies vesicle-associated membrane protein 1 (VAMP1), which encodes a critical protein for synaptic exocytosis, as the responsible gene. In total, 50 affected individuals from these families and three independent probands from Ontario (Canada) share the disease phenotype together with a disruptive VAMP1 mutation that affects a critical donor site for the splicing of VAMP1 isoforms. This mutation leads to the loss of the only VAMP1 isoform (VAMP1A) expressed in the nervous system, thus highlighting an association between the well-studied VAMP1 and a neurological disorder. Given the variable phenotype seen in the affected individuals examined here, we believe that VAMP1 should be tested for mutations in patients with either ataxia or spastic paraplegia.",

author = "Bourassa, {Cynthia V.} and Meijer, {Inge A.} and Merner, {Nancy D.} and Grewal, {Kanwal K.} and Stefanelli, {Mark G.} and Kathleen Hodgkinson and Ives, {Elizabeth J.} and William Pryse-Phillips and Mandar Jog and Kym Boycott and Grimes, {David A.} and Sharan Goobie and Richard Leckey and Dion, {Patrick A.} and Rouleau, {Guy A.}",

note = "Funding Information: The authors would like to thank the family members and the volunteer controls, as well as Roger Green for kindly providing the latter ones. We also thank Weichun Lin for information about the heterozygous mouse. Special thanks to Loubna Jouan and Anna Szuto for their technical assistance. C.V.B. is supported by the Canadian Institutes for Health Research through the Master{\textquoteright}s Award: Frederick Banting and Charles Best Canada Graduate Scholarships. G.A.R. holds the Canada Research Chair and a Jeanne et J. Louis Levesque Chair for the Genetics of Brain Diseases. ",

year = "2012",

month = sep,

day = "7",

doi = "10.1016/j.ajhg.2012.07.018",

language = "English",

volume = "91",

pages = "548--552",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - VAMP1 mutation causes dominant hereditary spastic ataxia in newfoundland families

AU - Bourassa, Cynthia V.

AU - Meijer, Inge A.

AU - Merner, Nancy D.

AU - Grewal, Kanwal K.

AU - Stefanelli, Mark G.

AU - Hodgkinson, Kathleen

AU - Ives, Elizabeth J.

AU - Pryse-Phillips, William

AU - Jog, Mandar

AU - Boycott, Kym

AU - Grimes, David A.

AU - Goobie, Sharan

AU - Leckey, Richard

AU - Dion, Patrick A.

AU - Rouleau, Guy A.

N1 - Funding Information: The authors would like to thank the family members and the volunteer controls, as well as Roger Green for kindly providing the latter ones. We also thank Weichun Lin for information about the heterozygous mouse. Special thanks to Loubna Jouan and Anna Szuto for their technical assistance. C.V.B. is supported by the Canadian Institutes for Health Research through the Master’s Award: Frederick Banting and Charles Best Canada Graduate Scholarships. G.A.R. holds the Canada Research Chair and a Jeanne et J. Louis Levesque Chair for the Genetics of Brain Diseases.

PY - 2012/9/7

Y1 - 2012/9/7

N2 - Our group previously described and mapped to chromosomal region 12p13 a form of dominantly inherited hereditary spastic ataxia (HSA) in three large Newfoundland (Canada) families. This report identifies vesicle-associated membrane protein 1 (VAMP1), which encodes a critical protein for synaptic exocytosis, as the responsible gene. In total, 50 affected individuals from these families and three independent probands from Ontario (Canada) share the disease phenotype together with a disruptive VAMP1 mutation that affects a critical donor site for the splicing of VAMP1 isoforms. This mutation leads to the loss of the only VAMP1 isoform (VAMP1A) expressed in the nervous system, thus highlighting an association between the well-studied VAMP1 and a neurological disorder. Given the variable phenotype seen in the affected individuals examined here, we believe that VAMP1 should be tested for mutations in patients with either ataxia or spastic paraplegia.

AB - Our group previously described and mapped to chromosomal region 12p13 a form of dominantly inherited hereditary spastic ataxia (HSA) in three large Newfoundland (Canada) families. This report identifies vesicle-associated membrane protein 1 (VAMP1), which encodes a critical protein for synaptic exocytosis, as the responsible gene. In total, 50 affected individuals from these families and three independent probands from Ontario (Canada) share the disease phenotype together with a disruptive VAMP1 mutation that affects a critical donor site for the splicing of VAMP1 isoforms. This mutation leads to the loss of the only VAMP1 isoform (VAMP1A) expressed in the nervous system, thus highlighting an association between the well-studied VAMP1 and a neurological disorder. Given the variable phenotype seen in the affected individuals examined here, we believe that VAMP1 should be tested for mutations in patients with either ataxia or spastic paraplegia.

UR - http://www.scopus.com/inward/record.url?scp=84866071490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866071490&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2012.07.018

DO - 10.1016/j.ajhg.2012.07.018

M3 - Article

C2 - 22958904

AN - SCOPUS:84866071490

SN - 0002-9297

VL - 91

SP - 548

EP - 552

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 3

ER -

VAMP1 mutation causes dominant hereditary spastic ataxia in newfoundland families

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

Access to Document

Other files and links

Fingerprint

Cite this