Hereditary spastic paraplegia 3A associated with axonal neuropathy

Neviana Ivanova; Kristl G Claeys; Tine Deconinck; Ivan Litvinenko; Albena Jordanova; Michaela Auer-Grumbach; Jana Haberlova; Ann Löfgren; Gisele Smeyers; Eva Nelis; Rudy Mercelis; Barbara Plecko; Josef Priller; Josef Zámecník; Berten Ceulemans; Anne Kjersti Erichsen; Erik Björck; Garth Nicholson; Michael W Sereda; Pavel Seeman; Ivo Kremensky; Vanio Mitev; Peter De Jonghe

doi:10.1001/archneur.64.5.706

Hereditary spastic paraplegia 3A associated with axonal neuropathy

Neviana Ivanova, Kristl G Claeys, Tine Deconinck, Ivan Litvinenko, Albena Jordanova, Michaela Auer-Grumbach, Jana Haberlova, Ann Löfgren, Gisele Smeyers, Eva Nelis, Rudy Mercelis, Barbara Plecko, Josef Priller, Josef Zámecník, Berten Ceulemans, Anne Kjersti Erichsen, Erik Björck, Garth Nicholson, Michael W Sereda, Pavel SeemanIvo Kremensky, Vanio Mitev, Peter De Jonghe

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

Abstract

OBJECTIVE: To study the frequency and distribution of mutations in SPG3A in a large cohort of patients with hereditary spastic paraplegia.

DESIGN: We screened a large cohort of 182 families and isolated cases with pure or complex hereditary spastic paraplegia phenotypes, which were negative for mutations in SPG4.

RESULTS: In 12 probands (6.6%), we identified 12 different SPG3A mutations (11 missense and 1 insertion/frameshift) of which 7 were novel and 3 were de novo. We found incomplete penetrance in 1 family (G482V). In most cases, SPG3A mutations were associated with an early age at onset (mean, 3 y); however, in 1 family (R495W mutation), symptoms started later (mean, 14 y) with clear intrafamilial variability (8-28 y). Six patients with an SPG3A mutation (F151S, Q191R, M408T, G469A, R495W) originating from 5 unrelated families presented with a complex form of hereditary spastic paraplegia associated with a neuropathy (17%). Our electrophysiological and pathological findings confirmed an axonal sensory-motor neuropathy. There was no correlation between the genotype and the presence of a neuropathy.

CONCLUSIONS: We conclude that mutations in SPG3A represent an important cause of patients in the overall hereditary spastic paraplegia population. SPG3A is more often associated with a neuropathy than previously assumed. Therefore, patients with a bipyramidal syndrome and a neuropathy should be screened for mutations in SPG3A.

Original language	English
Pages (from-to)	706-13
Number of pages	8
Journal	Archives of Neurology
Volume	64
Issue number	5
DOIs	https://doi.org/10.1001/archneur.64.5.706
Publication status	Published - May 2007

Keywords / Materials (for Non-textual outputs)

Adolescent
Adult
Age of Onset
Aged
Amides
Aminobutyrates
Butyrates
Child
Cohort Studies
DNA Mutational Analysis
Family Health
Female
Genetic Predisposition to Disease
Humans
Male
Membrane Proteins
Middle Aged
Mutation
Polyneuropathies
Spastic Paraplegia, Hereditary
Vesicular Transport Proteins
Journal Article
Research Support, Non-U.S. Gov't

Access to Document

10.1001/archneur.64.5.706

Cite this

Ivanova, N., Claeys, K. G., Deconinck, T., Litvinenko, I., Jordanova, A., Auer-Grumbach, M., Haberlova, J., Löfgren, A., Smeyers, G., Nelis, E., Mercelis, R., Plecko, B., Priller, J., Zámecník, J., Ceulemans, B., Erichsen, A. K., Björck, E., Nicholson, G., Sereda, M. W., ... De Jonghe, P. (2007). Hereditary spastic paraplegia 3A associated with axonal neuropathy. Archives of Neurology, 64(5), 706-13. https://doi.org/10.1001/archneur.64.5.706

@article{0a43bd42d22640768bdb53d9fee441d4,

title = "Hereditary spastic paraplegia 3A associated with axonal neuropathy",

abstract = "OBJECTIVE: To study the frequency and distribution of mutations in SPG3A in a large cohort of patients with hereditary spastic paraplegia.DESIGN: We screened a large cohort of 182 families and isolated cases with pure or complex hereditary spastic paraplegia phenotypes, which were negative for mutations in SPG4.RESULTS: In 12 probands (6.6%), we identified 12 different SPG3A mutations (11 missense and 1 insertion/frameshift) of which 7 were novel and 3 were de novo. We found incomplete penetrance in 1 family (G482V). In most cases, SPG3A mutations were associated with an early age at onset (mean, 3 y); however, in 1 family (R495W mutation), symptoms started later (mean, 14 y) with clear intrafamilial variability (8-28 y). Six patients with an SPG3A mutation (F151S, Q191R, M408T, G469A, R495W) originating from 5 unrelated families presented with a complex form of hereditary spastic paraplegia associated with a neuropathy (17%). Our electrophysiological and pathological findings confirmed an axonal sensory-motor neuropathy. There was no correlation between the genotype and the presence of a neuropathy.CONCLUSIONS: We conclude that mutations in SPG3A represent an important cause of patients in the overall hereditary spastic paraplegia population. SPG3A is more often associated with a neuropathy than previously assumed. Therefore, patients with a bipyramidal syndrome and a neuropathy should be screened for mutations in SPG3A.",

keywords = "Adolescent, Adult, Age of Onset, Aged, Amides, Aminobutyrates, Butyrates, Child, Cohort Studies, DNA Mutational Analysis, Family Health, Female, Genetic Predisposition to Disease, Humans, Male, Membrane Proteins, Middle Aged, Mutation, Polyneuropathies, Spastic Paraplegia, Hereditary, Vesicular Transport Proteins, Journal Article, Research Support, Non-U.S. Gov't",

author = "Neviana Ivanova and Claeys, {Kristl G} and Tine Deconinck and Ivan Litvinenko and Albena Jordanova and Michaela Auer-Grumbach and Jana Haberlova and Ann L{\"o}fgren and Gisele Smeyers and Eva Nelis and Rudy Mercelis and Barbara Plecko and Josef Priller and Josef Z{\'a}mecn{\'i}k and Berten Ceulemans and Erichsen, {Anne Kjersti} and Erik Bj{\"o}rck and Garth Nicholson and Sereda, {Michael W} and Pavel Seeman and Ivo Kremensky and Vanio Mitev and {De Jonghe}, Peter",

year = "2007",

month = may,

doi = "10.1001/archneur.64.5.706",

language = "English",

volume = "64",

pages = "706--13",

journal = "Archives of Neurology",

issn = "0003-9942",

publisher = "American Medical Association",

number = "5",

}

Ivanova, N, Claeys, KG, Deconinck, T, Litvinenko, I, Jordanova, A, Auer-Grumbach, M, Haberlova, J, Löfgren, A, Smeyers, G, Nelis, E, Mercelis, R, Plecko, B, Priller, J, Zámecník, J, Ceulemans, B, Erichsen, AK, Björck, E, Nicholson, G, Sereda, MW, Seeman, P, Kremensky, I, Mitev, V & De Jonghe, P 2007, 'Hereditary spastic paraplegia 3A associated with axonal neuropathy', Archives of Neurology, vol. 64, no. 5, pp. 706-13. https://doi.org/10.1001/archneur.64.5.706

TY - JOUR

T1 - Hereditary spastic paraplegia 3A associated with axonal neuropathy

AU - Ivanova, Neviana

AU - Claeys, Kristl G

AU - Deconinck, Tine

AU - Litvinenko, Ivan

AU - Jordanova, Albena

AU - Auer-Grumbach, Michaela

AU - Haberlova, Jana

AU - Löfgren, Ann

AU - Smeyers, Gisele

AU - Nelis, Eva

AU - Mercelis, Rudy

AU - Plecko, Barbara

AU - Priller, Josef

AU - Zámecník, Josef

AU - Ceulemans, Berten

AU - Erichsen, Anne Kjersti

AU - Björck, Erik

AU - Nicholson, Garth

AU - Sereda, Michael W

AU - Seeman, Pavel

AU - Kremensky, Ivo

AU - Mitev, Vanio

AU - De Jonghe, Peter

PY - 2007/5

Y1 - 2007/5

N2 - OBJECTIVE: To study the frequency and distribution of mutations in SPG3A in a large cohort of patients with hereditary spastic paraplegia.DESIGN: We screened a large cohort of 182 families and isolated cases with pure or complex hereditary spastic paraplegia phenotypes, which were negative for mutations in SPG4.RESULTS: In 12 probands (6.6%), we identified 12 different SPG3A mutations (11 missense and 1 insertion/frameshift) of which 7 were novel and 3 were de novo. We found incomplete penetrance in 1 family (G482V). In most cases, SPG3A mutations were associated with an early age at onset (mean, 3 y); however, in 1 family (R495W mutation), symptoms started later (mean, 14 y) with clear intrafamilial variability (8-28 y). Six patients with an SPG3A mutation (F151S, Q191R, M408T, G469A, R495W) originating from 5 unrelated families presented with a complex form of hereditary spastic paraplegia associated with a neuropathy (17%). Our electrophysiological and pathological findings confirmed an axonal sensory-motor neuropathy. There was no correlation between the genotype and the presence of a neuropathy.CONCLUSIONS: We conclude that mutations in SPG3A represent an important cause of patients in the overall hereditary spastic paraplegia population. SPG3A is more often associated with a neuropathy than previously assumed. Therefore, patients with a bipyramidal syndrome and a neuropathy should be screened for mutations in SPG3A.

AB - OBJECTIVE: To study the frequency and distribution of mutations in SPG3A in a large cohort of patients with hereditary spastic paraplegia.DESIGN: We screened a large cohort of 182 families and isolated cases with pure or complex hereditary spastic paraplegia phenotypes, which were negative for mutations in SPG4.RESULTS: In 12 probands (6.6%), we identified 12 different SPG3A mutations (11 missense and 1 insertion/frameshift) of which 7 were novel and 3 were de novo. We found incomplete penetrance in 1 family (G482V). In most cases, SPG3A mutations were associated with an early age at onset (mean, 3 y); however, in 1 family (R495W mutation), symptoms started later (mean, 14 y) with clear intrafamilial variability (8-28 y). Six patients with an SPG3A mutation (F151S, Q191R, M408T, G469A, R495W) originating from 5 unrelated families presented with a complex form of hereditary spastic paraplegia associated with a neuropathy (17%). Our electrophysiological and pathological findings confirmed an axonal sensory-motor neuropathy. There was no correlation between the genotype and the presence of a neuropathy.CONCLUSIONS: We conclude that mutations in SPG3A represent an important cause of patients in the overall hereditary spastic paraplegia population. SPG3A is more often associated with a neuropathy than previously assumed. Therefore, patients with a bipyramidal syndrome and a neuropathy should be screened for mutations in SPG3A.

KW - Adolescent

KW - Adult

KW - Age of Onset

KW - Aged

KW - Amides

KW - Aminobutyrates

KW - Butyrates

KW - Child

KW - Cohort Studies

KW - DNA Mutational Analysis

KW - Family Health

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Membrane Proteins

KW - Middle Aged

KW - Mutation

KW - Polyneuropathies

KW - Spastic Paraplegia, Hereditary

KW - Vesicular Transport Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1001/archneur.64.5.706

DO - 10.1001/archneur.64.5.706

M3 - Article

C2 - 17502470

SN - 0003-9942

VL - 64

SP - 706

EP - 713

JO - Archives of Neurology

JF - Archives of Neurology

IS - 5

ER -

Hereditary spastic paraplegia 3A associated with axonal neuropathy

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Cite this