Distal truncation of KCC3 in non-French Canadian HMSN/ACC families

A. Salin-Cantegrel, J. B. Rivière, N. Dupré, F. M. Charron, M. Shekarabi, L. Karéméra, C. Gaspar, J. Horst, Mustafa Tekin, G. Deda, A. Krause, M. M. Lippert, M. A A P Willemsen, R. Jarrar, J. Y. Lapointe, G. A. Rouleau

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

BACKGROUND: Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a severe and progressive autosomal recessive polyneuropathy. Mutations in the potassium-chloride cotransporter 3 gene (KCC3) were identified as responsible for HMSN/ACC in the French Canadian (FC) population. In the present study, the authors were interested in finding new mutations in non-FC populations, assessing the activity of mutant proteins and refining genotype-phenotype correlations. METHODS: The authors screened KCC3 for mutations using direct sequencing in six non-FC HMSN/ACC families. They then assessed the functionality of the most common mutant protein using a flux assay in Xenopus laevis oocytes. RESULTS: The authors identified mutations in exon 22 of KCC3: a novel mutation (del + 2994-3003; E1015X) in one family, as well as a known mutation (3031C→T; R1011X) found in five unrelated families and associated with two different haplotypes. The function of the cotransporter was abolished, although a limited amount of mutant proteins were correctly localized at the membrane. CONCLUSIONS: KCC3 mutations in exon 22 constitute a recurrent mutation site for hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), regardless of ethnic origin, and are the most common cause of HMSN/ACC in the non-French Canadian (FC) families analyzed so far. Therefore, for genetic analysis, exon 22 screening should be prioritized in non-FC populations. Finally, the R1011X mutation leads to the abrogation of KCC3's function in Xenopus laevis oocytes, likely due to impaired transit of the cotransporter.

Original languageEnglish
Pages (from-to)1350-1355
Number of pages6
JournalNeurology
Volume69
Issue number13
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

Fingerprint

Mutation
Mutant Proteins
Exons
Xenopus laevis
Oocytes
Population
Corpus callosum agenesis neuronopathy
Polyneuropathies
Genetic Association Studies
Haplotypes
Membranes
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Salin-Cantegrel, A., Rivière, J. B., Dupré, N., Charron, F. M., Shekarabi, M., Karéméra, L., ... Rouleau, G. A. (2007). Distal truncation of KCC3 in non-French Canadian HMSN/ACC families. Neurology, 69(13), 1350-1355. https://doi.org/10.1212/01.wnl.0000291779.35643.15

Distal truncation of KCC3 in non-French Canadian HMSN/ACC families. / Salin-Cantegrel, A.; Rivière, J. B.; Dupré, N.; Charron, F. M.; Shekarabi, M.; Karéméra, L.; Gaspar, C.; Horst, J.; Tekin, Mustafa; Deda, G.; Krause, A.; Lippert, M. M.; Willemsen, M. A A P; Jarrar, R.; Lapointe, J. Y.; Rouleau, G. A.

In: Neurology, Vol. 69, No. 13, 01.09.2007, p. 1350-1355.

Research output: Contribution to journalArticle

Salin-Cantegrel, A, Rivière, JB, Dupré, N, Charron, FM, Shekarabi, M, Karéméra, L, Gaspar, C, Horst, J, Tekin, M, Deda, G, Krause, A, Lippert, MM, Willemsen, MAAP, Jarrar, R, Lapointe, JY & Rouleau, GA 2007, 'Distal truncation of KCC3 in non-French Canadian HMSN/ACC families', Neurology, vol. 69, no. 13, pp. 1350-1355. https://doi.org/10.1212/01.wnl.0000291779.35643.15
Salin-Cantegrel A, Rivière JB, Dupré N, Charron FM, Shekarabi M, Karéméra L et al. Distal truncation of KCC3 in non-French Canadian HMSN/ACC families. Neurology. 2007 Sep 1;69(13):1350-1355. https://doi.org/10.1212/01.wnl.0000291779.35643.15
Salin-Cantegrel, A. ; Rivière, J. B. ; Dupré, N. ; Charron, F. M. ; Shekarabi, M. ; Karéméra, L. ; Gaspar, C. ; Horst, J. ; Tekin, Mustafa ; Deda, G. ; Krause, A. ; Lippert, M. M. ; Willemsen, M. A A P ; Jarrar, R. ; Lapointe, J. Y. ; Rouleau, G. A. / Distal truncation of KCC3 in non-French Canadian HMSN/ACC families. In: Neurology. 2007 ; Vol. 69, No. 13. pp. 1350-1355.
@article{f268f34afd424219a326689156287983,
title = "Distal truncation of KCC3 in non-French Canadian HMSN/ACC families",
abstract = "BACKGROUND: Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a severe and progressive autosomal recessive polyneuropathy. Mutations in the potassium-chloride cotransporter 3 gene (KCC3) were identified as responsible for HMSN/ACC in the French Canadian (FC) population. In the present study, the authors were interested in finding new mutations in non-FC populations, assessing the activity of mutant proteins and refining genotype-phenotype correlations. METHODS: The authors screened KCC3 for mutations using direct sequencing in six non-FC HMSN/ACC families. They then assessed the functionality of the most common mutant protein using a flux assay in Xenopus laevis oocytes. RESULTS: The authors identified mutations in exon 22 of KCC3: a novel mutation (del + 2994-3003; E1015X) in one family, as well as a known mutation (3031C→T; R1011X) found in five unrelated families and associated with two different haplotypes. The function of the cotransporter was abolished, although a limited amount of mutant proteins were correctly localized at the membrane. CONCLUSIONS: KCC3 mutations in exon 22 constitute a recurrent mutation site for hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), regardless of ethnic origin, and are the most common cause of HMSN/ACC in the non-French Canadian (FC) families analyzed so far. Therefore, for genetic analysis, exon 22 screening should be prioritized in non-FC populations. Finally, the R1011X mutation leads to the abrogation of KCC3's function in Xenopus laevis oocytes, likely due to impaired transit of the cotransporter.",
author = "A. Salin-Cantegrel and Rivi{\`e}re, {J. B.} and N. Dupr{\'e} and Charron, {F. M.} and M. Shekarabi and L. Kar{\'e}m{\'e}ra and C. Gaspar and J. Horst and Mustafa Tekin and G. Deda and A. Krause and Lippert, {M. M.} and Willemsen, {M. A A P} and R. Jarrar and Lapointe, {J. Y.} and Rouleau, {G. A.}",
year = "2007",
month = "9",
day = "1",
doi = "10.1212/01.wnl.0000291779.35643.15",
language = "English",
volume = "69",
pages = "1350--1355",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "13",

}

TY - JOUR

T1 - Distal truncation of KCC3 in non-French Canadian HMSN/ACC families

AU - Salin-Cantegrel, A.

AU - Rivière, J. B.

AU - Dupré, N.

AU - Charron, F. M.

AU - Shekarabi, M.

AU - Karéméra, L.

AU - Gaspar, C.

AU - Horst, J.

AU - Tekin, Mustafa

AU - Deda, G.

AU - Krause, A.

AU - Lippert, M. M.

AU - Willemsen, M. A A P

AU - Jarrar, R.

AU - Lapointe, J. Y.

AU - Rouleau, G. A.

PY - 2007/9/1

Y1 - 2007/9/1

N2 - BACKGROUND: Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a severe and progressive autosomal recessive polyneuropathy. Mutations in the potassium-chloride cotransporter 3 gene (KCC3) were identified as responsible for HMSN/ACC in the French Canadian (FC) population. In the present study, the authors were interested in finding new mutations in non-FC populations, assessing the activity of mutant proteins and refining genotype-phenotype correlations. METHODS: The authors screened KCC3 for mutations using direct sequencing in six non-FC HMSN/ACC families. They then assessed the functionality of the most common mutant protein using a flux assay in Xenopus laevis oocytes. RESULTS: The authors identified mutations in exon 22 of KCC3: a novel mutation (del + 2994-3003; E1015X) in one family, as well as a known mutation (3031C→T; R1011X) found in five unrelated families and associated with two different haplotypes. The function of the cotransporter was abolished, although a limited amount of mutant proteins were correctly localized at the membrane. CONCLUSIONS: KCC3 mutations in exon 22 constitute a recurrent mutation site for hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), regardless of ethnic origin, and are the most common cause of HMSN/ACC in the non-French Canadian (FC) families analyzed so far. Therefore, for genetic analysis, exon 22 screening should be prioritized in non-FC populations. Finally, the R1011X mutation leads to the abrogation of KCC3's function in Xenopus laevis oocytes, likely due to impaired transit of the cotransporter.

AB - BACKGROUND: Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a severe and progressive autosomal recessive polyneuropathy. Mutations in the potassium-chloride cotransporter 3 gene (KCC3) were identified as responsible for HMSN/ACC in the French Canadian (FC) population. In the present study, the authors were interested in finding new mutations in non-FC populations, assessing the activity of mutant proteins and refining genotype-phenotype correlations. METHODS: The authors screened KCC3 for mutations using direct sequencing in six non-FC HMSN/ACC families. They then assessed the functionality of the most common mutant protein using a flux assay in Xenopus laevis oocytes. RESULTS: The authors identified mutations in exon 22 of KCC3: a novel mutation (del + 2994-3003; E1015X) in one family, as well as a known mutation (3031C→T; R1011X) found in five unrelated families and associated with two different haplotypes. The function of the cotransporter was abolished, although a limited amount of mutant proteins were correctly localized at the membrane. CONCLUSIONS: KCC3 mutations in exon 22 constitute a recurrent mutation site for hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), regardless of ethnic origin, and are the most common cause of HMSN/ACC in the non-French Canadian (FC) families analyzed so far. Therefore, for genetic analysis, exon 22 screening should be prioritized in non-FC populations. Finally, the R1011X mutation leads to the abrogation of KCC3's function in Xenopus laevis oocytes, likely due to impaired transit of the cotransporter.

UR - http://www.scopus.com/inward/record.url?scp=34748886205&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34748886205&partnerID=8YFLogxK

U2 - 10.1212/01.wnl.0000291779.35643.15

DO - 10.1212/01.wnl.0000291779.35643.15

M3 - Article

C2 - 17893295

AN - SCOPUS:34748886205

VL - 69

SP - 1350

EP - 1355

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 13

ER -