Learn More
Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination(More)
OBJECTIVE Hereditary spastic paraplegias (HSPs) are very heterogeneous inherited neurodegenerative disorders. Our group recently identified ZFYVE26 as the gene responsible for one of the clinical and genetic entities, SPG15. Our aim was to describe its clinical and mutational spectra. METHODS We analyzed all exons of SPG15/ZFYVE26 gene by direct(More)
Hereditary spastic paraplegias (HSP) are neurodegenerative diseases mainly characterized by lower limb spasticity associated, in complicated forms, with additional neurological signs. We have analysed a large series of index patients (n = 76) with this condition, either from families with an autosomal recessive inheritance (n = 43) or isolated patients (n =(More)
BACKGROUND Deletions in ITPR1, coding for the inositol-triphosphate receptor type 1, have been recently identified in spinocerebellar ataxia type 15 (SCA15). OBJECTIVE To determine the frequency and the phenotypical spectrum of SCA15. DESIGN Taqman polymerase chain reaction (258 index cases) or single-nucleotide polymorphism genome-wide genotyping (75(More)
Reliable and easy to perform functional scales are a prerequisite for future therapeutic trials in cerebellar ataxias. In order to assess the specificity of quantitative functional tests of cerebellar dysfunction, we investigated 123 controls, 141 patients with an autosomal dominant cerebellar ataxia (ADCA) and 53 patients with autosomal dominant spastic(More)
BACKGROUND At least 28 loci have been linked to autosomal dominant spinocerebellar ataxia (ADCA). Causative genes have been cloned for 10 nucleotide repeat expansions (SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and 31) and six genes with classical mutations (SCA5, 13, 14, 15/16, 27 and 28). Recently, a large British pedigree linked to SCA11 has been reported to carry(More)
BACKGROUND Transgenes are often engineered using regulatory elements from distantly related genomes. Although correct expression patterns are frequently achieved even in transgenic mice, inappropriate expression, especially with promoters of widely expressed genes, has been reported. DNA methylation has been implicated in the aberrant expression, but the(More)
Glypicans are essential modulators of cell signalling during embryogenesis. Little is known about their functions in brain development. We show here that mouse glypicans (gpc-1 to gpc-6) are differentially expressed in embryonic brains during key morphogenetic events. In gastrulating embryos, gpc-4 is the only glypican expressed in anterior visceral(More)
IMPORTANCE Autosomal recessive cerebellar ataxia type I, also known as recessive ataxia of Beauce, is a slowly progressive ataxia that leads to moderate disability with gait ataxia, dysarthria, dysmetria, mild oculomotor abnormalities, and diffuse cerebellar atrophy on brain imaging. Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene, located(More)
Polyglutamine-coding (CAG)n repeat expansions in seven different genes cause spinocerebellar ataxias. Although the size of the expansion is negatively correlated with age at onset, it accounts for only 50-70% of its variability. To find other factors involved in this variability, we performed a regression analysis in 1255 affected individuals with(More)