The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Norio Niikawa - One of the best experts on this subject based on the ideXlab platform.
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Exclusion mapping of the Cohen Syndrome gene from the Prader‐Willi Syndrome locus
Clinical genetics, 2008Co-Authors: Ikuko Kondo, Jun-ichi Hamabe, Kohtaro Yamamoto, Norio NiikawaAbstract:Karyotype and DNA analyses using DNA probes were carried out in a family with the Cohen Syndrome. Two affected brothers had normal chromosomal constitutions. A major deletion or duplication of genomic DNA fragments hybridized with the DNA probes, pML34 at D15S9 locus and pTD3-21 at D15S10 locus, assigned on 15q11-q12 was not detected in the patients. In addition, a linkage of the Syndrome to D15S9 and D15S10 loci was not observed in the family. These data suggest that a gene for the Cohen Syndrome is excluded from the 15q11-q12 region, on which a gene for the Prader-Willi Syndrome is assigned, and that the Cohen Syndrome is distinctly different from the Prader-Willi Syndrome, although clinical manifestations of the Cohen and the Prader-Willi Syndromes are very similar.
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exclusion mapping of the Cohen Syndrome gene from the prader willi Syndrome locus
Clinical Genetics, 2008Co-Authors: Ikuko Kondo, Jun-ichi Hamabe, Kohtaro Yamamoto, Norio NiikawaAbstract:Karyotype and DNA analyses using DNA probes were carried out in a family with the Cohen Syndrome. Two affected brothers had normal chromosomal constitutions. A major deletion or duplication of genomic DNA fragments hybridized with the DNA probes, pML34 at D15S9 locus and pTD3-21 at D15S10 locus, assigned on 15q11-q12 was not detected in the patients. In addition, a linkage of the Syndrome to D15S9 and D15S10 loci was not observed in the family. These data suggest that a gene for the Cohen Syndrome is excluded from the 15q11-q12 region, on which a gene for the Prader-Willi Syndrome is assigned, and that the Cohen Syndrome is distinctly different from the Prader-Willi Syndrome, although clinical manifestations of the Cohen and the Prader-Willi Syndromes are very similar.
Ikuko Kondo - One of the best experts on this subject based on the ideXlab platform.
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Exclusion mapping of the Cohen Syndrome gene from the Prader‐Willi Syndrome locus
Clinical genetics, 2008Co-Authors: Ikuko Kondo, Jun-ichi Hamabe, Kohtaro Yamamoto, Norio NiikawaAbstract:Karyotype and DNA analyses using DNA probes were carried out in a family with the Cohen Syndrome. Two affected brothers had normal chromosomal constitutions. A major deletion or duplication of genomic DNA fragments hybridized with the DNA probes, pML34 at D15S9 locus and pTD3-21 at D15S10 locus, assigned on 15q11-q12 was not detected in the patients. In addition, a linkage of the Syndrome to D15S9 and D15S10 loci was not observed in the family. These data suggest that a gene for the Cohen Syndrome is excluded from the 15q11-q12 region, on which a gene for the Prader-Willi Syndrome is assigned, and that the Cohen Syndrome is distinctly different from the Prader-Willi Syndrome, although clinical manifestations of the Cohen and the Prader-Willi Syndromes are very similar.
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exclusion mapping of the Cohen Syndrome gene from the prader willi Syndrome locus
Clinical Genetics, 2008Co-Authors: Ikuko Kondo, Jun-ichi Hamabe, Kohtaro Yamamoto, Norio NiikawaAbstract:Karyotype and DNA analyses using DNA probes were carried out in a family with the Cohen Syndrome. Two affected brothers had normal chromosomal constitutions. A major deletion or duplication of genomic DNA fragments hybridized with the DNA probes, pML34 at D15S9 locus and pTD3-21 at D15S10 locus, assigned on 15q11-q12 was not detected in the patients. In addition, a linkage of the Syndrome to D15S9 and D15S10 loci was not observed in the family. These data suggest that a gene for the Cohen Syndrome is excluded from the 15q11-q12 region, on which a gene for the Prader-Willi Syndrome is assigned, and that the Cohen Syndrome is distinctly different from the Prader-Willi Syndrome, although clinical manifestations of the Cohen and the Prader-Willi Syndromes are very similar.
Jun-ichi Hamabe - One of the best experts on this subject based on the ideXlab platform.
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Exclusion mapping of the Cohen Syndrome gene from the Prader‐Willi Syndrome locus
Clinical genetics, 2008Co-Authors: Ikuko Kondo, Jun-ichi Hamabe, Kohtaro Yamamoto, Norio NiikawaAbstract:Karyotype and DNA analyses using DNA probes were carried out in a family with the Cohen Syndrome. Two affected brothers had normal chromosomal constitutions. A major deletion or duplication of genomic DNA fragments hybridized with the DNA probes, pML34 at D15S9 locus and pTD3-21 at D15S10 locus, assigned on 15q11-q12 was not detected in the patients. In addition, a linkage of the Syndrome to D15S9 and D15S10 loci was not observed in the family. These data suggest that a gene for the Cohen Syndrome is excluded from the 15q11-q12 region, on which a gene for the Prader-Willi Syndrome is assigned, and that the Cohen Syndrome is distinctly different from the Prader-Willi Syndrome, although clinical manifestations of the Cohen and the Prader-Willi Syndromes are very similar.
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exclusion mapping of the Cohen Syndrome gene from the prader willi Syndrome locus
Clinical Genetics, 2008Co-Authors: Ikuko Kondo, Jun-ichi Hamabe, Kohtaro Yamamoto, Norio NiikawaAbstract:Karyotype and DNA analyses using DNA probes were carried out in a family with the Cohen Syndrome. Two affected brothers had normal chromosomal constitutions. A major deletion or duplication of genomic DNA fragments hybridized with the DNA probes, pML34 at D15S9 locus and pTD3-21 at D15S10 locus, assigned on 15q11-q12 was not detected in the patients. In addition, a linkage of the Syndrome to D15S9 and D15S10 loci was not observed in the family. These data suggest that a gene for the Cohen Syndrome is excluded from the 15q11-q12 region, on which a gene for the Prader-Willi Syndrome is assigned, and that the Cohen Syndrome is distinctly different from the Prader-Willi Syndrome, although clinical manifestations of the Cohen and the Prader-Willi Syndromes are very similar.
Kohtaro Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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Exclusion mapping of the Cohen Syndrome gene from the Prader‐Willi Syndrome locus
Clinical genetics, 2008Co-Authors: Ikuko Kondo, Jun-ichi Hamabe, Kohtaro Yamamoto, Norio NiikawaAbstract:Karyotype and DNA analyses using DNA probes were carried out in a family with the Cohen Syndrome. Two affected brothers had normal chromosomal constitutions. A major deletion or duplication of genomic DNA fragments hybridized with the DNA probes, pML34 at D15S9 locus and pTD3-21 at D15S10 locus, assigned on 15q11-q12 was not detected in the patients. In addition, a linkage of the Syndrome to D15S9 and D15S10 loci was not observed in the family. These data suggest that a gene for the Cohen Syndrome is excluded from the 15q11-q12 region, on which a gene for the Prader-Willi Syndrome is assigned, and that the Cohen Syndrome is distinctly different from the Prader-Willi Syndrome, although clinical manifestations of the Cohen and the Prader-Willi Syndromes are very similar.
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exclusion mapping of the Cohen Syndrome gene from the prader willi Syndrome locus
Clinical Genetics, 2008Co-Authors: Ikuko Kondo, Jun-ichi Hamabe, Kohtaro Yamamoto, Norio NiikawaAbstract:Karyotype and DNA analyses using DNA probes were carried out in a family with the Cohen Syndrome. Two affected brothers had normal chromosomal constitutions. A major deletion or duplication of genomic DNA fragments hybridized with the DNA probes, pML34 at D15S9 locus and pTD3-21 at D15S10 locus, assigned on 15q11-q12 was not detected in the patients. In addition, a linkage of the Syndrome to D15S9 and D15S10 loci was not observed in the family. These data suggest that a gene for the Cohen Syndrome is excluded from the 15q11-q12 region, on which a gene for the Prader-Willi Syndrome is assigned, and that the Cohen Syndrome is distinctly different from the Prader-Willi Syndrome, although clinical manifestations of the Cohen and the Prader-Willi Syndromes are very similar.
Wenke Seifert - One of the best experts on this subject based on the ideXlab platform.
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Cohen Syndrome associated protein coh1 physically and functionally interacts with the small gtpase rab6 at the golgi complex and directs neurite outgrowth
Journal of Biological Chemistry, 2015Co-Authors: Wenke Seifert, Stefanie Lommatzsch, Tanja Maritzen, Denise Horn, Hans Christian Hennies, Sebastian Bachmann, Jirko Kühnisch, Volker HauckeAbstract:Abstract Postnatal microcephaly, intellectual disability, and progressive retinal dystrophy are major features of autosomal recessive Cohen Syndrome, which is caused by mutations in the gene COH1 (VPS13B). We have recently identified COH1 as a Golgi-enriched scaffold protein that contributes to the structural maintenance and function of the Golgi complex. Here, we show that association of COH1 with the Golgi complex depends on the small GTPase RAB6. RNAi-mediated knockdown of RAB6A/A′ prevents the localization of COH1 to the Golgi complex. Expression of the constitutively inactive RAB6_T27N mutant led to an increased solubilization of COH1 from lipid membrane preparations. Co-IP experiments confirmed the physical interaction of COH1 with RAB6 that preferentially occurred with the constitutively active RAB6_Q72L mutants. Depletion of COH1 in primary neurons negatively interfered with neurite outgrowth, indicating a causal link between the integrity of the Golgi complex and axonal outgrowth. We conclude that COH1 is a RAB6 effector protein and that reduced brain size in Cohen Syndrome patients likely results from impaired COH1 function at the Golgi complex, causing decreased neuritogenesis.
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Cohen Syndrome-associated Protein, COH1, Is a Novel, Giant Golgi Matrix Protein Required for Golgi Integrity
The Journal of biological chemistry, 2011Co-Authors: Wenke Seifert, Tanja Maritzen, Volker Haucke, Denise Horn, Jirko Kühnisch, Hans Christian HenniesAbstract:Loss-of-function mutations in the gene COH1, also known as VPS13B, lead to autosomal recessive Cohen Syndrome. However, the cellular distribution and function of the encoded protein COH1 (3997 amino acids), which lacks functional homologies to other mammalian proteins, have remained enigmatic. We show here that COH1 is a peripheral Golgi membrane protein that strongly co-localizes with the cis-Golgi matrix protein GM130. Consistent with its subcellular localization, COH1 depletion using RNAi causes fragmentation of the Golgi ribbon into ministacks. Disruption of Golgi organization observed in fibroblasts from Cohen Syndrome patients suggests that Golgi dysfunction contributes to Cohen Syndrome pathology. In conclusion, our findings establish COH1 as a Golgi-associated matrix protein required for Golgi integrity.
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Expanded Mutational Spectrum in Cohen Syndrome, Tissue Expression, and Transcript Variants of COH1
Human mutation, 2008Co-Authors: Wenke Seifert, Jirko Kühnisch, Andreas Tzschach, Masoud Garshasbi, Muriel Holder-espinasse, Kimia Kahrizi, Hossein Najmabadi, Andreas W. Kuss, Wolfram Kress, Genevieve LaureysAbstract:Cohen Syndrome is characterised by mental retardation, postnatal microcephaly, facial dysmorphism, pigmentary retinopathy, myopia, and intermittent neutropenia. Mutations in COH1 (VPS13B) have been found in patients with Cohen Syndrome from diverse ethnic origins. We have carried out mutation analysis in twelve novel patients with Cohen Syndrome from nine families. In this series, we have identified 13 different mutations in COH1, twelve of these are novel including six frameshift mutations, four nonsense mutations, two splice site mutations, and a one-codon deletion. Since different transcripts of COH1 have been reported previously, we have analysed the expression patterns of COH1 splice variants. The transcript variant NM_152564 including exon 28b showed ubiquitous expression in all examined human tissues. In contrast, human brain and retina showed differential splicing of exon 28 (NM_017890). Moreover, analysis of mouse tissues revealed ubiquitous expression of Coh1 homologous to human NM_152564 in all examined tissues but no prevalent alternative splicing. (C) 2008 Wiley-Liss, Inc.
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Allelic heterogeneity in the COH1 gene explains clinical variability in Cohen Syndrome.
American journal of human genetics, 2004Co-Authors: Hans Christian Hennies, Wenke Seifert, Anita Rauch, Christian Schumi, Elisabeth Moser, Eva Al-taji, Gholamali Tariverdian, Krystyna H. Chrzanowska, Małgorzata Krajewska-walasek, Anna RajabAbstract:Cohen Syndrome is a rare autosomal recessive disorder with a variable clinical picture mainly characterized by developmental delay, mental retardation, microcephaly, typical facial dysmorphism, progressive pigmentary retinopathy, severe myopia, and intermittent neutropenia. A Cohen Syndrome locus was mapped to chromosome 8q22 in Finnish patients, and, recently, mutations in the gene COH1 were reported in patients with Cohen Syndrome from Finland and other parts of northern and western Europe. Here, we describe clinical and molecular findings in 20 patients with Cohen Syndrome from 12 families, originating from Brazil, Germany, Lebanon, Oman, Poland, and Turkey. All patients were homozygous or compound heterozygous for mutations in COH1. We identified a total of 17 novel mutations, mostly resulting in premature termination codons. The clinical presentation was highly variable. Developmental delay of varying degree, early-onset myopia, joint laxity, and facial dysmorphism were the only features present in all patients; however, retinopathy at school age, microcephaly, and neutropenia are not requisite symptoms of Cohen Syndrome. The identification of novel mutations in COH1 in an ethnically diverse group of patients demonstrates extensive allelic heterogeneity and explains the intriguing clinical variability in Cohen Syndrome.