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Alteration of Ganglioside Biosynthesis Responsible for Complex Hereditary Spastic Paraplegia
- Source :
- The American journal of human genetics 93(1), 118-123 (2013). doi:10.1016/j.ajhg.2013.05.006
- Publication Year :
- 2013
- Publisher :
- Elsevier, 2013.
-
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.
- Subjects :
- Male
biosynthesis [Gangliosides]
0302 clinical medicine
Gangliosides
Germany
Spastic
Missense mutation
Genetics(clinical)
Exome
Age of Onset
Child
Genetics (clinical)
Genetics
0303 health sciences
genetics [Cerebellar Ataxia]
Homozygote
Chromosome Mapping
methods [Chromosome Mapping]
Galactosyltransferases
3. Good health
Pedigree
Child, Preschool
Female
medicine.symptom
Brazil
Adult
Tunisia
Adolescent
Cerebellar Ataxia
Hereditary spastic paraplegia
Mutation, Missense
Locus (genetics)
Biology
genetics [Gangliosides]
genetics [Galactosyltransferases]
03 medical and health sciences
Young Adult
Genetic linkage
ddc:570
genetics [Spastic Paraplegia, Hereditary]
Report
medicine
Humans
Cognitive Dysfunction
Genetic Predisposition to Disease
030304 developmental biology
Cerebellar ataxia
Portugal
Spastic Paraplegia, Hereditary
genetics [Cognitive Dysfunction]
Infant
medicine.disease
beta-1,4-galactosyltransferase I
Lipid Metabolism
Hyperintensity
Spain
metabolism [Spastic Paraplegia, Hereditary]
metabolism [Galactosyltransferases]
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- The American journal of human genetics 93(1), 118-123 (2013). doi:10.1016/j.ajhg.2013.05.006
- Accession number :
- edsair.doi.dedup.....88db94d58828441f2ac429d276d3ef52