The Experts below are selected from a list of 1554 Experts worldwide ranked by ideXlab platform
Alexandra Durr - One of the best experts on this subject based on the ideXlab platform.
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Spinocerebellar ataxia with sensory neuropathy (SCA25).
The Cerebellum, 2020Co-Authors: Giovanni Stevanin, Nathalie Streichenberger, Nicolas Kopp, Emmanuel Broussolle, Alexis Brice, Alexandra DurrAbstract:Spinocerebellar ataxia 25 (SCA25) is a rare form of autosomal dominant cerebellar ataxia associated with a severe sensory neuropathy. Clinical variability ranges from incomplete penetrance at age 61 to a Friedreich ataxia-like syndrome. The responsible locus was mapped to Chromosome 2p in a large region of 14 Mbases in a single French kindred.
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spinocerebellar ataxia with sensory neuropathy sca25 maps to Chromosome 2p
Annals of Neurology, 2004Co-Authors: Giovanni Stevanin, Emmanuel Broussolle, Alexandra Durr, Naima Bouslam, Stephane Thobois, Hamid Azzedine, Lucas Ravaux, Anne Boland, Martin Schalling, Alexis BriceAbstract:Autosomal dominant cerebellar ataxias constitute one of the most clinically, neuropathologically, and genetically heterogeneous groups of neurodegenerative disorders. Approximately 50 to 80% of the families carry mutations in genes known to be implicated in spinocerebellar ataxias (SCAs). Numerous loci (SCAn) also have been mapped, often in single families, but the responsible genes have not yet been identified. This suggests further genetic heterogeneity. We have ascertained 18 subjects from a large French family in which cerebellar ataxia and prominent sensory neuropathy segregated as a dominant trait. Intrafamilial variability was high regarding age at onset (17 months to 39 years), severity, and the clinical picture that ranged from pure sensory neuropathy with little cerebellar involvement to a Friedreich's ataxia-like phenotype. After excluding known genes/loci responsible for SCA and hereditary sensory neuropathies, we detected linkage with Chromosome 2p markers in a genomewide screen. We designated this new locus SCA25 after testing of 16 additional markers. Maximum two-point logarithm of odds scores of 3.15 and 3.10 were obtained at D2S2378 and D2S2734, respectively. Haplotype analysis defined a critical 12.6cM region of 15Mb between D2S2174 and D2S2736. No linkage to this locus was found in four other families. This interval contains several genes that could be responsible for the disease. One of these genes, CRIPT, encodes a postsynaptic protein, but no mutations were found by direct sequencing, excluding its responsibility in the disease. CAG repeat expansions often are involved in SCA pathogenesis, but no pathological expansions were found at the protein or at the DNA level using the 1C2 antibody and the repeat expansion detection method, respectively. The gene responsible for SCA25 remains to be identified.
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A New Locus for Autosomal Dominant Pure Spastic Paraplegia, on Chromosome 2q24-q34
American Journal of Human Genetics, 2000Co-Authors: B Fontaine, Alexandra Durr, Jean Weissenbach, Jamile Hazan, Clairesophie Davoine, Caroline Paternotte, Imed Feki, Alexis BriceAbstract:Summary Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous disorders causing progressive spasticity and weakness of the lower limbs. We report a large family of French descent with autosomal dominant pure HSP. We excluded genetic linkage to the known loci causing HSP and performed a genomewide search. We found evidence for linkage of the disorder to polymorphic markers on Chromosome 2q24-q34: a maximum LOD score of 3.03 was obtained for marker D2S2318. By comparison with families having linkage to the major locus of pure autosomal dominant HSP (SPG4 on Chromosome 2p), there were significantly more patients without Babinski signs, with increased reflexes in the upper limbs, and with severe functional handicaps.
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linkage of a new locus for autosomal dominant familial spastic paraplegia to Chromosome 2p
Human Molecular Genetics, 1994Co-Authors: Alexandra Durr, Jamile Hazan, R.p.m. Bruyn, B Fontaine, C Lamy, Judith C T Van Deutekom, Clalresophie Rime, Judith Melkl, O LyoncaenAbstract:: Autosomal dominant familial spastic paraplegia (AD-FSP) is a genetically heterogeneous neurodegenerative disorder characterized by a spasticity of the lower limbs. A locus causing AD-FSP (FSP1) has been previously mapped to Chromosome 14q. We now report linkage of a second AD-FSP locus (FSP2) to Chromosome 2p21-p24 in five of seven French families and one large Dutch pedigree. The analysis of recombination events and multipoint linkage place FSP2 within a 4 cM interval flanked by loci D2S400 and D2S367.
Alexis Brice - One of the best experts on this subject based on the ideXlab platform.
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Spinocerebellar ataxia with sensory neuropathy (SCA25).
The Cerebellum, 2020Co-Authors: Giovanni Stevanin, Nathalie Streichenberger, Nicolas Kopp, Emmanuel Broussolle, Alexis Brice, Alexandra DurrAbstract:Spinocerebellar ataxia 25 (SCA25) is a rare form of autosomal dominant cerebellar ataxia associated with a severe sensory neuropathy. Clinical variability ranges from incomplete penetrance at age 61 to a Friedreich ataxia-like syndrome. The responsible locus was mapped to Chromosome 2p in a large region of 14 Mbases in a single French kindred.
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spinocerebellar ataxia with sensory neuropathy sca25 maps to Chromosome 2p
Annals of Neurology, 2004Co-Authors: Giovanni Stevanin, Emmanuel Broussolle, Alexandra Durr, Naima Bouslam, Stephane Thobois, Hamid Azzedine, Lucas Ravaux, Anne Boland, Martin Schalling, Alexis BriceAbstract:Autosomal dominant cerebellar ataxias constitute one of the most clinically, neuropathologically, and genetically heterogeneous groups of neurodegenerative disorders. Approximately 50 to 80% of the families carry mutations in genes known to be implicated in spinocerebellar ataxias (SCAs). Numerous loci (SCAn) also have been mapped, often in single families, but the responsible genes have not yet been identified. This suggests further genetic heterogeneity. We have ascertained 18 subjects from a large French family in which cerebellar ataxia and prominent sensory neuropathy segregated as a dominant trait. Intrafamilial variability was high regarding age at onset (17 months to 39 years), severity, and the clinical picture that ranged from pure sensory neuropathy with little cerebellar involvement to a Friedreich's ataxia-like phenotype. After excluding known genes/loci responsible for SCA and hereditary sensory neuropathies, we detected linkage with Chromosome 2p markers in a genomewide screen. We designated this new locus SCA25 after testing of 16 additional markers. Maximum two-point logarithm of odds scores of 3.15 and 3.10 were obtained at D2S2378 and D2S2734, respectively. Haplotype analysis defined a critical 12.6cM region of 15Mb between D2S2174 and D2S2736. No linkage to this locus was found in four other families. This interval contains several genes that could be responsible for the disease. One of these genes, CRIPT, encodes a postsynaptic protein, but no mutations were found by direct sequencing, excluding its responsibility in the disease. CAG repeat expansions often are involved in SCA pathogenesis, but no pathological expansions were found at the protein or at the DNA level using the 1C2 antibody and the repeat expansion detection method, respectively. The gene responsible for SCA25 remains to be identified.
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A New Locus for Autosomal Dominant Pure Spastic Paraplegia, on Chromosome 2q24-q34
American Journal of Human Genetics, 2000Co-Authors: B Fontaine, Alexandra Durr, Jean Weissenbach, Jamile Hazan, Clairesophie Davoine, Caroline Paternotte, Imed Feki, Alexis BriceAbstract:Summary Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous disorders causing progressive spasticity and weakness of the lower limbs. We report a large family of French descent with autosomal dominant pure HSP. We excluded genetic linkage to the known loci causing HSP and performed a genomewide search. We found evidence for linkage of the disorder to polymorphic markers on Chromosome 2q24-q34: a maximum LOD score of 3.03 was obtained for marker D2S2318. By comparison with families having linkage to the major locus of pure autosomal dominant HSP (SPG4 on Chromosome 2p), there were significantly more patients without Babinski signs, with increased reflexes in the upper limbs, and with severe functional handicaps.
Jamile Hazan - One of the best experts on this subject based on the ideXlab platform.
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A New Locus for Autosomal Dominant Pure Spastic Paraplegia, on Chromosome 2q24-q34
American Journal of Human Genetics, 2000Co-Authors: B Fontaine, Alexandra Durr, Jean Weissenbach, Jamile Hazan, Clairesophie Davoine, Caroline Paternotte, Imed Feki, Alexis BriceAbstract:Summary Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous disorders causing progressive spasticity and weakness of the lower limbs. We report a large family of French descent with autosomal dominant pure HSP. We excluded genetic linkage to the known loci causing HSP and performed a genomewide search. We found evidence for linkage of the disorder to polymorphic markers on Chromosome 2q24-q34: a maximum LOD score of 3.03 was obtained for marker D2S2318. By comparison with families having linkage to the major locus of pure autosomal dominant HSP (SPG4 on Chromosome 2p), there were significantly more patients without Babinski signs, with increased reflexes in the upper limbs, and with severe functional handicaps.
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a fine integrated map of the spg4 locus excludes an expanded cag repeat in Chromosome 2p linked autosomal dominant spastic paraplegia
Genomics, 1999Co-Authors: Jamile Hazan, Clairesophie Davoine, Delphine Mavel, Nuria Fonknechten, Caroline Paternotte, Cecile Fizames, Corinne Cruaud, Delphine Samson, Delphine Muselet, Nathalie VegaczarnyAbstract:Abstract Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a genetically heterogeneous disorder characterized by progressive spasticity of the lower limbs. A major locus (SPG4) causing AD-HSP in about 40% of the families was mapped to Chromosome 2p. The analysis of six SPG4-linked AD-HSP families using the RED procedure previously showed the expansion of a CAG repeat in affected individuals. To identify the gene responsible for this form of HSP, we have constructed a 3.5-Mb YAC contig flanked by loci D2S400 and D2S367, have subcloned five of these YACs spanning the candidate region into cosmids, and screened these cosmid libraries for the presence of CAG repeat sequences. Four CAG repeats have been identified but none of them is expanded in 26 patients from 13 SPG4-linked AD-HSP families. A gene map comprising 21 transcripts was established using expressed sequence tags (ESTs) assigned previously to this region of 2p21–p22 with radiation hybrid panels GeneBridge 4 and G3. Full-length cDNAs corresponding to the 14 ESTs mapping to the SPG4 interval flanked by loci D2S352 and D2S2347 were isolated and sequenced. None contains a CAG repeat in its coding sequence. Finally, we have assembled a BAC contig composed of 37 clones that were also screened for the presence of CAG repeats; this failed to detect additional repeats to those identified on YACs.
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mapping of a complicated familial spastic paraplegia to locus spg4 on Chromosome 2p
Journal of Medical Genetics, 1998Co-Authors: O Heinzlef, Jean Weissenbach, Caroline Paternotte, F Mahieux, J F Prudhomme, J Dien, M Madigand, J Pouget, E Roullet, Jamile HazanAbstract:Autosomal dominant familial spastic paraplegia (AD-FSP) is a degenerative disorder of the central motor system characterised by progressive spasticity of the lower limbs. AD-FSP has been divided into pure and complicated forms. Pure AD-FSP is genetically heterogeneous; three loci have been mapped to Chromosomes 14q (SPG3), 2p (SPG4), and 15q (SPG6), whereas no loci responsible for complicated forms have been identified to date. Here we report linkage to the SPG4 locus in a three generation family with AD-FSP complicated by dementia and epilepsy. Assuming that both forms of AD-FSP are caused by mutations involving the same FSP gene, analysis of recombination events in this family positions the SPG4 gene within a 0 cM interval flanked by loci D2S2255 and D2S2347.
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Autosomal dominant spastic paraplegia with anticipation maps to a 4-cM interval on Chromosome 2p21-p24 in a large German family*
Human Genetics, 1996Co-Authors: Joachim Bürger, Jamile Hazan, Caroline Paternotte, Hermann Metzke, Frank Schilling, André ReisAbstract:Autosomal dominant familial spastic paraplegias (AD-FSP) are a group of genetically heterogeneous diseases characterised by a progressive spasticity of the lower limbs. Three loci have already been identified by genetic linkage studies on Chromosomes 2p, 14q and 15q. Here we present linkage data from a large German family displaying AD-FSP with anticipation which confirms the existence of the FSP2 locus on Chromosome 2p. The recombination events observed in our family define the critical region for the FSP2 gene to be within a 4-cM interval, flanked by markers D2S400 and D2S367. Moreover, clinical data from our family show evidence of anticipation, a phenomenon caused by trinucleotide expansion in several other neurodegenerative diseases.
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linkage of a new locus for autosomal dominant familial spastic paraplegia to Chromosome 2p
Human Molecular Genetics, 1994Co-Authors: Alexandra Durr, Jamile Hazan, R.p.m. Bruyn, B Fontaine, C Lamy, Judith C T Van Deutekom, Clalresophie Rime, Judith Melkl, O LyoncaenAbstract:: Autosomal dominant familial spastic paraplegia (AD-FSP) is a genetically heterogeneous neurodegenerative disorder characterized by a spasticity of the lower limbs. A locus causing AD-FSP (FSP1) has been previously mapped to Chromosome 14q. We now report linkage of a second AD-FSP locus (FSP2) to Chromosome 2p21-p24 in five of seven French families and one large Dutch pedigree. The analysis of recombination events and multipoint linkage place FSP2 within a 4 cM interval flanked by loci D2S400 and D2S367.
Giovanni Stevanin - One of the best experts on this subject based on the ideXlab platform.
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Spinocerebellar ataxia with sensory neuropathy (SCA25).
The Cerebellum, 2020Co-Authors: Giovanni Stevanin, Nathalie Streichenberger, Nicolas Kopp, Emmanuel Broussolle, Alexis Brice, Alexandra DurrAbstract:Spinocerebellar ataxia 25 (SCA25) is a rare form of autosomal dominant cerebellar ataxia associated with a severe sensory neuropathy. Clinical variability ranges from incomplete penetrance at age 61 to a Friedreich ataxia-like syndrome. The responsible locus was mapped to Chromosome 2p in a large region of 14 Mbases in a single French kindred.
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spinocerebellar ataxia with sensory neuropathy sca25 maps to Chromosome 2p
Annals of Neurology, 2004Co-Authors: Giovanni Stevanin, Emmanuel Broussolle, Alexandra Durr, Naima Bouslam, Stephane Thobois, Hamid Azzedine, Lucas Ravaux, Anne Boland, Martin Schalling, Alexis BriceAbstract:Autosomal dominant cerebellar ataxias constitute one of the most clinically, neuropathologically, and genetically heterogeneous groups of neurodegenerative disorders. Approximately 50 to 80% of the families carry mutations in genes known to be implicated in spinocerebellar ataxias (SCAs). Numerous loci (SCAn) also have been mapped, often in single families, but the responsible genes have not yet been identified. This suggests further genetic heterogeneity. We have ascertained 18 subjects from a large French family in which cerebellar ataxia and prominent sensory neuropathy segregated as a dominant trait. Intrafamilial variability was high regarding age at onset (17 months to 39 years), severity, and the clinical picture that ranged from pure sensory neuropathy with little cerebellar involvement to a Friedreich's ataxia-like phenotype. After excluding known genes/loci responsible for SCA and hereditary sensory neuropathies, we detected linkage with Chromosome 2p markers in a genomewide screen. We designated this new locus SCA25 after testing of 16 additional markers. Maximum two-point logarithm of odds scores of 3.15 and 3.10 were obtained at D2S2378 and D2S2734, respectively. Haplotype analysis defined a critical 12.6cM region of 15Mb between D2S2174 and D2S2736. No linkage to this locus was found in four other families. This interval contains several genes that could be responsible for the disease. One of these genes, CRIPT, encodes a postsynaptic protein, but no mutations were found by direct sequencing, excluding its responsibility in the disease. CAG repeat expansions often are involved in SCA pathogenesis, but no pathological expansions were found at the protein or at the DNA level using the 1C2 antibody and the repeat expansion detection method, respectively. The gene responsible for SCA25 remains to be identified.
Monica Colombo - One of the best experts on this subject based on the ideXlab platform.
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Chromosome 2p gain in monoclonal b cell lymphocytosis and in early stage chronic lymphocytic leukemia
American Journal of Hematology, 2013Co-Authors: Sonia Fabris, Laura Mosca, Giovanna Cutrona, Marta Lionetti, Luca Agnelli, Gabriella Ciceri, Marzia Barbieri, Francesco Maura, Serena Matis, Monica ColomboAbstract:Recent studies have described Chromosome 2p gain as a recurrent lesion in chronic lymphocytic leukemia (CLL). We investigated the 2p gain and its relationship with common prognostic biomarkers in a prospective series of 69 clinical monoclonal B-cell lymphocytosis (cMBL) and 218 early stage (Binet A) CLL patients. The 2p gain was detected by FISH in 17 patients (6%, 16 CLL, and 1 cMBL) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e., del(11)(q23) and del(17)(p13) (P = 0.002), were significantly more frequent in 2p gain cases, as well as unmutated status of IGHV (P < 1 × 10−4) and CD38 (P < 1 × 10−4) and ZAP-70 positive expression (P = 0.003). Furthermore, 2p gain patients had significantly higher utilization of stereotyped B-cell receptors compared with 2p negative patients (P = 0.009), and the incidence of stereotyped subset #1 in 2p gain patients was significantly higher than that found in the remaining CLLs (P = 0.031). Transcriptional profiling analysis identified several genes significantly upregulated in 2p gain CLLs, most of which mapped to 2p. Among these, NCOA1 and ROCK2 are known for their involvement in tumor progression in several human cancers, whereas among those located in different Chromosomes, CAV1 at 7q31.1 has been recently identified to play a critical role in CLL progression. Thus, 2p gain can be present since the early stages of the disease, particularly in those cases characterized by other poor prognosis markers. The finding of genes upregulated in the cells with 2p gain provides new insights to define the pathogenic role of this lesion. Am. J. Hematol. 2013. © 2012 Wiley Periodicals, Inc.
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Chromosome 2p gain in monoclonal B‐cell lymphocytosis and in early stage chronic lymphocytic leukemia
American Journal of Hematology, 2012Co-Authors: Sonia Fabris, Laura Mosca, Giovanna Cutrona, Marta Lionetti, Luca Agnelli, Gabriella Ciceri, Marzia Barbieri, Francesco Maura, Serena Matis, Monica ColomboAbstract:Recent studies have described Chromosome 2p gain as a recurrent lesion in chronic lymphocytic leukemia (CLL). We investigated the 2p gain and its relationship with common prognostic biomarkers in a prospective series of 69 clinical monoclonal B-cell lymphocytosis (cMBL) and 218 early stage (Binet A) CLL patients. The 2p gain was detected by FISH in 17 patients (6%, 16 CLL, and 1 cMBL) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e., del(11)(q23) and del(17)(p13) (P = 0.002), were significantly more frequent in 2p gain cases, as well as unmutated status of IGHV (P < 1 × 10−4) and CD38 (P < 1 × 10−4) and ZAP-70 positive expression (P = 0.003). Furthermore, 2p gain patients had significantly higher utilization of stereotyped B-cell receptors compared with 2p negative patients (P = 0.009), and the incidence of stereotyped subset #1 in 2p gain patients was significantly higher than that found in the remaining CLLs (P = 0.031). Transcriptional profiling analysis identified several genes significantly upregulated in 2p gain CLLs, most of which mapped to 2p. Among these, NCOA1 and ROCK2 are known for their involvement in tumor progression in several human cancers, whereas among those located in different Chromosomes, CAV1 at 7q31.1 has been recently identified to play a critical role in CLL progression. Thus, 2p gain can be present since the early stages of the disease, particularly in those cases characterized by other poor prognosis markers. The finding of genes upregulated in the cells with 2p gain provides new insights to define the pathogenic role of this lesion. Am. J. Hematol. 2013. © 2012 Wiley Periodicals, Inc.