Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia

Amir Boukhris, Rebecca Schule, José L. Loureiro, Charles Marques Lourenço, Emeline Mundwiller, Michael A. Gonzalez, Perrine Charles, Julie Gauthier, Imen Rekik, Rafael F. Acosta Lebrigio, Marion Gaussen, Fiorella Speziani, Andreas Ferbert, Imed Feki, Andrés Caballero-Oteyza, Alexandre Dionne-Laporte, Mohamed Amri, Anne Noreau, Sylvie Forlani, Vitor T. Cruz & 13 others Fanny Mochel, Paula Coutinho, Patrick Dion, Chokri Mhiri, Ludger Schols, Jean Pouget, Frédéric Darios, Guy A. Rouleau, Wilson Marques, Alexis Brice, Alexandra Durr, Stephan L Zuchner, Giovanni Stevanin

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Hereditary spastic paraplegias (HSPs) form a heterogeneous group of neurological disorders. A whole-genome linkage mapping effort was made with three HSP-affected families from Spain, Portugal, and Tunisia and it allowed us to reduce the SPG26 locus interval from 34 to 9 Mb. Subsequently, a targeted capture was made to sequence the entire exome of affected individuals from these three families, as well as from two additional autosomal-recessive HSP-affected families of German and Brazilian origins. Five homozygous truncating (n = 3) and missense (n = 2) mutations were identified in B4GALNT1. After this finding, we analyzed the entire coding region of this gene in 65 additional cases, and three mutations were identified in two subjects. All mutated cases presented an early-onset spastic paraplegia, with frequent intellectual disability, cerebellar ataxia, and peripheral neuropathy as well as cortical atrophy and white matter hyperintensities on brain imaging. B4GALNT1 encodes β-1,4-N-acetyl-galactosaminyl transferase 1 (B4GALNT1), involved in ganglioside biosynthesis. These findings confirm the increasing interest of lipid metabolism in HSPs. Interestingly, although the catabolism of gangliosides is implicated in a variety of neurological diseases, SPG26 is only the second human disease involving defects of their biosynthesis.

Original languageEnglish
Pages (from-to)118-123
Number of pages6
JournalAmerican Journal of Human Genetics
Volume93
Issue number1
DOIs
StatePublished - Jul 11 2013

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Hereditary Spastic Paraplegia
Gangliosides
Chromosome Mapping
Exome
Tunisia
Cerebellar Ataxia
Mutation
Portugal
Paraplegia
Peripheral Nervous System Diseases
Transferases
Nervous System Diseases
Lipid Metabolism
Neuroimaging
Intellectual Disability
Spain
Atrophy
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Boukhris, A., Schule, R., Loureiro, J. L., Lourenço, C. M., Mundwiller, E., Gonzalez, M. A., ... Stevanin, G. (2013). Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. American Journal of Human Genetics, 93(1), 118-123. https://doi.org/10.1016/j.ajhg.2013.05.006

Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. / Boukhris, Amir; Schule, Rebecca; Loureiro, José L.; Lourenço, Charles Marques; Mundwiller, Emeline; Gonzalez, Michael A.; Charles, Perrine; Gauthier, Julie; Rekik, Imen; Acosta Lebrigio, Rafael F.; Gaussen, Marion; Speziani, Fiorella; Ferbert, Andreas; Feki, Imed; Caballero-Oteyza, Andrés; Dionne-Laporte, Alexandre; Amri, Mohamed; Noreau, Anne; Forlani, Sylvie; Cruz, Vitor T.; Mochel, Fanny; Coutinho, Paula; Dion, Patrick; Mhiri, Chokri; Schols, Ludger; Pouget, Jean; Darios, Frédéric; Rouleau, Guy A.; Marques, Wilson; Brice, Alexis; Durr, Alexandra; Zuchner, Stephan L; Stevanin, Giovanni.

In: American Journal of Human Genetics, Vol. 93, No. 1, 11.07.2013, p. 118-123.

Research output: Contribution to journalArticle

Boukhris, A, Schule, R, Loureiro, JL, Lourenço, CM, Mundwiller, E, Gonzalez, MA, Charles, P, Gauthier, J, Rekik, I, Acosta Lebrigio, RF, Gaussen, M, Speziani, F, Ferbert, A, Feki, I, Caballero-Oteyza, A, Dionne-Laporte, A, Amri, M, Noreau, A, Forlani, S, Cruz, VT, Mochel, F, Coutinho, P, Dion, P, Mhiri, C, Schols, L, Pouget, J, Darios, F, Rouleau, GA, Marques, W, Brice, A, Durr, A, Zuchner, SL & Stevanin, G 2013, 'Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia', American Journal of Human Genetics, vol. 93, no. 1, pp. 118-123. https://doi.org/10.1016/j.ajhg.2013.05.006
Boukhris A, Schule R, Loureiro JL, Lourenço CM, Mundwiller E, Gonzalez MA et al. Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. American Journal of Human Genetics. 2013 Jul 11;93(1):118-123. https://doi.org/10.1016/j.ajhg.2013.05.006
Boukhris, Amir ; Schule, Rebecca ; Loureiro, José L. ; Lourenço, Charles Marques ; Mundwiller, Emeline ; Gonzalez, Michael A. ; Charles, Perrine ; Gauthier, Julie ; Rekik, Imen ; Acosta Lebrigio, Rafael F. ; Gaussen, Marion ; Speziani, Fiorella ; Ferbert, Andreas ; Feki, Imed ; Caballero-Oteyza, Andrés ; Dionne-Laporte, Alexandre ; Amri, Mohamed ; Noreau, Anne ; Forlani, Sylvie ; Cruz, Vitor T. ; Mochel, Fanny ; Coutinho, Paula ; Dion, Patrick ; Mhiri, Chokri ; Schols, Ludger ; Pouget, Jean ; Darios, Frédéric ; Rouleau, Guy A. ; Marques, Wilson ; Brice, Alexis ; Durr, Alexandra ; Zuchner, Stephan L ; Stevanin, Giovanni. / Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. In: American Journal of Human Genetics. 2013 ; Vol. 93, No. 1. pp. 118-123.
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AU - Lourenço, Charles Marques

AU - Mundwiller, Emeline

AU - Gonzalez, Michael A.

AU - Charles, Perrine

AU - Gauthier, Julie

AU - Rekik, Imen

AU - Acosta Lebrigio, Rafael F.

AU - Gaussen, Marion

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AU - Ferbert, Andreas

AU - Feki, Imed

AU - Caballero-Oteyza, Andrés

AU - Dionne-Laporte, Alexandre

AU - Amri, Mohamed

AU - Noreau, Anne

AU - Forlani, Sylvie

AU - Cruz, Vitor T.

AU - Mochel, Fanny

AU - Coutinho, Paula

AU - Dion, Patrick

AU - Mhiri, Chokri

AU - Schols, Ludger

AU - Pouget, Jean

AU - Darios, Frédéric

AU - Rouleau, Guy A.

AU - Marques, Wilson

AU - Brice, Alexis

AU - Durr, Alexandra

AU - Zuchner, Stephan L

AU - Stevanin, Giovanni

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