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 language | English |
|---|---|
| Pages (from-to) | 118-123 |
| Number of pages | 6 |
| Journal | American Journal of Human Genetics |
| Volume | 93 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 11 2013 |
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ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia
AU - Boukhris, Amir
AU - Schule, Rebecca
AU - Loureiro, José L.
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
AU - Speziani, Fiorella
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
PY - 2013/7/11
Y1 - 2013/7/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajhg.2013.05.006
DO - 10.1016/j.ajhg.2013.05.006
M3 - Article
VL - 93
SP - 118
EP - 123
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 1
ER -