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  1. Article: Potential added value of a RT-qPCR method of SOX 11 expression, in the context of a multidisciplinary diagnostic assessment of B cell malignancies.

    Magne, Julien / Jenvrin, Alizée / Chauchet, Adrien / Casasnovas, Olivier / Donzel, Anne / Jego, Laurence / Aral, Bernard / Guy, Julien / Nadal, Nathalie / Vernerey, Dewi / Callier, Patrick / Garnache-Ottou, Francine / Ferrand, Christophe

    Experimental hematology & oncology

    2018  Volume 7, Page(s) 5

    Abstract: Background: Expression of SRY [sex-determining region Y]-box11 (SOX11) is specific to mantle cell lymphoma (MCL) and contributes, in conjunction with immunoglobulin variable heavy chain gene mutation status, to the identification of two forms of this ... ...

    Abstract Background: Expression of SRY [sex-determining region Y]-box11 (SOX11) is specific to mantle cell lymphoma (MCL) and contributes, in conjunction with immunoglobulin variable heavy chain gene mutation status, to the identification of two forms of this disease.
    Methods: The aim of this report was firstly, to design an easy and suitable RT-qPCR method to quantify SOX11 mRNA expression in mantle cell lymphoma and other B cell malignancies with the proper reference gene; secondly, to define the best threshold of relative quantity of SOX11 mRNA in order to reach the best compromise between sensitivity and specificity.
    Results: For best discrimination of MCL and non-MCL groups we determined an area under the curve (AUC) of 0.9750 and a threshold of 1.76 with 100% sensitivity and 88% specificity. AUC and threshold values of respectively 0.91/1.346 [87% sensitivity, 80% specificity] and 0.9525/1.7120 [100% sensitivity, 88% specificity] for GAPDH and RPLP0 respectively denote that the RPLP0 reference gene alone is sufficient for PCR housekeeping gene.
    Conclusion: This work describes an RT-qPCR assay for SOX11 expression in order to better characterize MCL at diagnosis. Further studies on larger cohorts are needed to evaluate this molecular tool, especially for the follow-up of minimal residual disease.
    Language English
    Publishing date 2018-02-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2669066-4
    ISSN 2162-3619
    ISSN 2162-3619
    DOI 10.1186/s40164-018-0097-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Smoking and FOS expression from blood leukocyte transcripts in patients with coronary artery disease.

    Saliques, Sebastien / Teyssier, Jean-Raymond / Vergely, Catherine / Lorgis, Luc / Lorin, Julie / Donzel, Anne / Sicard, Pierre / Berchoud, Juliane / Ragot, Sylviane / Touzery, Claude / Cottin, Yves / Rochette, Luc / Zeller, Marianne

    Atherosclerosis

    2011  Volume 219, Issue 2, Page(s) 931–936

    Abstract: Objective: Analysis of the leukocyte transriptome, in particular the Finkel-Biskis-Jinkins Osteosarcoma (c-Fos) gene, which has a prominent role in inflammation, provides new insights into atherosclerosis mechanisms. Although smoking is a major risk ... ...

    Abstract Objective: Analysis of the leukocyte transriptome, in particular the Finkel-Biskis-Jinkins Osteosarcoma (c-Fos) gene, which has a prominent role in inflammation, provides new insights into atherosclerosis mechanisms. Although smoking is a major risk factor, the links between smoking status and coronary artery disease (CAD) remains unclear. We aimed to analyze the relationship between smoking status and c-Fos expression in circulating leukocytes of patients with CAD.
    Methods: c-Fos expression was measured by RT-Q-PCR, from blood leukocytes of 239 consecutive patients after acute myocardial infarction (MI). The patients were asked about their smoking status and stratified into 3 groups: current smokers (CS) (N = 85), past smokers (PS) (N = 78) and never smokers (NS) (N = 76).
    Results: NS had a higher risk profile including hypertension, and CS were younger than PS and NS (-13 years and 17 years respectively). There was only a trend towards lower CRP levels in NS and PS than in CS. The mean c-Fos transcript level was slightly higher in CS than in PS and NS (0.924 vs. 0.908 and 0.861 AU, respectively; p = 0.005). By univariate analysis, neither age, nor sex, nor CRP nor white blood cell count was associated with c-Fos transcript levels. By multivariate analysis, CS (vs. PS + NS) was the strongest predictor of the c-Fos transcript level, (B = 0.042 ± 0.014, p = 0.003), even after adjustment for confounding factors (i.e. hypertension, chronic medication, family history of CAD, and prior MI).
    Conclusion: Our work suggests that c-Fos transcript level in blood leukocyte could be considered a cumulative biomarker of smoking. As the c-Fos gene has been put forward as a new factor in the progression and severity of atherosclerosis, it could be considered a novel potential pathway of tobacco toxicity in coronary artery disease.
    MeSH term(s) Aged ; Aged, 80 and over ; Chi-Square Distribution ; Coronary Angiography ; Coronary Artery Disease/blood ; Coronary Artery Disease/diagnostic imaging ; Coronary Artery Disease/etiology ; Coronary Artery Disease/genetics ; Female ; France ; Genes, fos ; Genetic Markers ; Humans ; Inflammation Mediators/blood ; Leukocytes/metabolism ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Myocardial Infarction/blood ; Myocardial Infarction/diagnostic imaging ; Myocardial Infarction/etiology ; Myocardial Infarction/genetics ; Prospective Studies ; RNA, Messenger/blood ; Risk Assessment ; Risk Factors ; Smoking/adverse effects ; Smoking Cessation ; Smoking Prevention
    Chemical Substances Genetic Markers ; Inflammation Mediators ; RNA, Messenger
    Language English
    Publishing date 2011-12
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80061-2
    ISSN 1879-1484 ; 0021-9150
    ISSN (online) 1879-1484
    ISSN 0021-9150
    DOI 10.1016/j.atherosclerosis.2011.09.026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Circulating leukocyte telomere length and oxidative stress: a new target for statin therapy.

    Saliques, Sebastien / Teyssier, Jean-Raymond / Vergely, Catherine / Lorgis, Luc / Lorin, Julie / Farnier, Michel / Donzel, Anne / Sicard, Pierre / Berchoud, Juliane / Lagrost, Anne-Cécile / Touzery, Claude / Ragot, Sylviane / Cottin, Yves / Rochette, Luc / Zeller, Marianne

    Atherosclerosis

    2011  Volume 219, Issue 2, Page(s) 753–760

    Abstract: Objectives: We investigated the relationship between prior statin therapy and leukocyte telomere length (LTL), as well as their interaction with potential new biomarkers of oxidative deoxyribonucleic acid (DNA) lesions and reactive oxygen species- ... ...

    Abstract Objectives: We investigated the relationship between prior statin therapy and leukocyte telomere length (LTL), as well as their interaction with potential new biomarkers of oxidative deoxyribonucleic acid (DNA) lesions and reactive oxygen species-induced inflammation.
    Methods and results: From patients admitted for an acute myocardial infarction, LTL was assessed by quantitative polymerase chain reaction (Q-PCR), and leukocyte Finkel-Biskis-Jinkins osteosarcoma (FOS) and 8-oxoguanine DNA glycosylase (OGG1) messenger ribonucleic acid (mRNA) levels were measured by retrotranscription Q-PCR. Patients under prior chronic statin therapy were compared with patients without statin therapy. Although patients on statin therapy were older, their mean LTL was longer than patients not under statin therapy (1.29 ± 0.11 vs. 1.25 ± 0.11 T/S ratio, p = 0.008). In contrast, FOS and OGG1 mRNA levels were similar for the 2 groups. LTL decreased with increasing age, FOS, and OGG1 mRNA levels. Statin therapy remained associated with longer LTL, even after adjustment for confounding factors (p = 0.001), and in younger patients (≤ 64 y). Even in groups matched for propensity scores for statin use, LTL was markedly longer in patients under statin therapy.
    Conclusions: Our observational study showed that statin therapy was associated with longer LTL. These data bring to light opportunities to identify new targets for early primary preventive treatment strategies. Moreover, our study raised FOS and OGG1 as new relevant biomarkers of LTL.
    MeSH term(s) Aged ; Aged, 80 and over ; Chi-Square Distribution ; DNA Glycosylases/genetics ; Dyslipidemias/blood ; Dyslipidemias/complications ; Dyslipidemias/drug therapy ; Dyslipidemias/genetics ; Female ; Genetic Markers ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Leukocytes/drug effects ; Leukocytes/metabolism ; Linear Models ; Logistic Models ; Male ; Middle Aged ; Myocardial Infarction/blood ; Myocardial Infarction/genetics ; Myocardial Infarction/prevention & control ; Oxidative Stress/drug effects ; Propensity Score ; Proto-Oncogene Proteins c-fos/genetics ; RNA, Messenger/blood ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Assessment ; Risk Factors ; Telomere/drug effects ; Telomere/metabolism
    Chemical Substances Genetic Markers ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Proto-Oncogene Proteins c-fos ; RNA, Messenger ; DNA Glycosylases (EC 3.2.2.-) ; oxoguanine glycosylase 1, human (EC 3.2.2.-)
    Language English
    Publishing date 2011-12
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80061-2
    ISSN 1879-1484 ; 0021-9150
    ISSN (online) 1879-1484
    ISSN 0021-9150
    DOI 10.1016/j.atherosclerosis.2011.09.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Smoking and FOS expression from blood leukocyte transcripts in patients with coronary artery disease

    Saliques, Sebastien / Teyssier, Jean-Raymond / Vergely, Catherine / Lorgis, Luc / Lorin, Julie / Donzel, Anne / Sicard, Pierre / Berchoud, Juliane / Ragot, Sylviane / Touzery, Claude / Cottin, Yves / Rochette, Luc / Zeller, Marianne

    Atherosclerosis. 2011 Dec., v. 219, no. 2

    2011  

    Abstract: OBJECTIVE: Analysis of the leukocyte transriptome, in particular the Finkel-Biskis-Jinkins Osteosarcoma (c-Fos) gene, which has a prominent role in inflammation, provides new insights into atherosclerosis mechanisms. Although smoking is a major risk ... ...

    Abstract OBJECTIVE: Analysis of the leukocyte transriptome, in particular the Finkel-Biskis-Jinkins Osteosarcoma (c-Fos) gene, which has a prominent role in inflammation, provides new insights into atherosclerosis mechanisms. Although smoking is a major risk factor, the links between smoking status and coronary artery disease (CAD) remains unclear. We aimed to analyze the relationship between smoking status and c-Fos expression in circulating leukocytes of patients with CAD. METHODS: c-Fos expression was measured by RT-Q-PCR, from blood leukocytes of 239 consecutive patients after acute myocardial infarction (MI). The patients were asked about their smoking status and stratified into 3 groups: current smokers (CS) (N=85), past smokers (PS) (N=78) and never smokers (NS) (N=76). RESULTS: NS had a higher risk profile including hypertension, and CS were younger than PS and NS (−13 years and 17 years respectively). There was only a trend towards lower CRP levels in NS and PS than in CS. The mean c-Fos transcript level was slightly higher in CS than in PS and NS (0.924 vs. 0.908 and 0.861AU, respectively; p=0.005). By univariate analysis, neither age, nor sex, nor CRP nor white blood cell count was associated with c-Fos transcript levels. By multivariate analysis, CS (vs. PS+NS) was the strongest predictor of the c-Fos transcript level, (B=0.042±0.014, p=0.003), even after adjustment for confounding factors (i.e. hypertension, chronic medication, family history of CAD, and prior MI). CONCLUSION: Our work suggests that c-Fos transcript level in blood leukocyte could be considered a cumulative biomarker of smoking. As the c-Fos gene has been put forward as a new factor in the progression and severity of atherosclerosis, it could be considered a novel potential pathway of tobacco toxicity in coronary artery disease.
    Keywords atherosclerosis ; biomarkers ; coronary artery disease ; drug therapy ; genes ; hypertension ; inflammation ; leukocyte count ; leukocytes ; multivariate analysis ; myocardial infarction ; osteosarcoma ; patients ; risk factors ; risk profile ; tobacco ; toxicity
    Language English
    Dates of publication 2011-12
    Size p. 931-936.
    Publishing place Elsevier Ireland Ltd
    Document type Article
    ZDB-ID 80061-2
    ISSN 1879-1484 ; 0021-9150
    ISSN (online) 1879-1484
    ISSN 0021-9150
    DOI 10.1016/j.atherosclerosis.2011.09.026
    Database NAL-Catalogue (AGRICOLA)

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  5. Article: Circulating leukocyte telomere length and oxidative stress: A new target for statin therapy

    Saliques, Sebastien / Teyssier, Jean-Raymond / Vergely, Catherine / Lorgis, Luc / Lorin, Julie / Farnier, Michel / Donzel, Anne / Sicard, Pierre / Berchoud, Juliane / Lagrost, Anne-Cécile / Touzery, Claude / Ragot, Sylviane / Cottin, Yves / Rochette, Luc / Zeller, Marianne

    Atherosclerosis. 2011 Dec., v. 219, no. 2

    2011  

    Abstract: OBJECTIVES: We investigated the relationship between prior statin therapy and leukocyte telomere length (LTL), as well as their interaction with potential new biomarkers of oxidative deoxyribonucleic acid (DNA) lesions and reactive oxygen species-induced ...

    Abstract OBJECTIVES: We investigated the relationship between prior statin therapy and leukocyte telomere length (LTL), as well as their interaction with potential new biomarkers of oxidative deoxyribonucleic acid (DNA) lesions and reactive oxygen species-induced inflammation. METHODS AND RESULTS: From patients admitted for an acute myocardial infarction, LTL was assessed by quantitative polymerase chain reaction (Q-PCR), and leukocyte Finkel-Biskis-Jinkins osteosarcoma (FOS) and 8-oxoguanine DNA glycosylase (OGG1) messenger ribonucleic acid (mRNA) levels were measured by retrotranscription Q-PCR. Patients under prior chronic statin therapy were compared with patients without statin therapy. Although patients on statin therapy were older, their mean LTL was longer than patients not under statin therapy (1.29±0.11 vs. 1.25±0.11 T/S ratio, p=0.008). In contrast, FOS and OGG1 mRNA levels were similar for the 2 groups. LTL decreased with increasing age, FOS, and OGG1 mRNA levels. Statin therapy remained associated with longer LTL, even after adjustment for confounding factors (p=0.001), and in younger patients (≤64y). Even in groups matched for propensity scores for statin use, LTL was markedly longer in patients under statin therapy. CONCLUSIONS: Our observational study showed that statin therapy was associated with longer LTL. These data bring to light opportunities to identify new targets for early primary preventive treatment strategies. Moreover, our study raised FOS and OGG1 as new relevant biomarkers of LTL.
    Keywords DNA ; atherosclerosis ; biomarkers ; inflammation ; messenger RNA ; myocardial infarction ; observational studies ; osteosarcoma ; oxidative stress ; oxygen ; patients ; quantitative polymerase chain reaction ; telomeres ; therapeutics
    Language English
    Dates of publication 2011-12
    Size p. 753-760.
    Publishing place Elsevier Ireland Ltd
    Document type Article
    ZDB-ID 80061-2
    ISSN 1879-1484 ; 0021-9150
    ISSN (online) 1879-1484
    ISSN 0021-9150
    DOI 10.1016/j.atherosclerosis.2011.09.011
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Search for genomic imbalances in a cohort of 20 patients with oral-facial-digital syndromes negative for mutations and large rearrangements in the OFD1 gene.

    Thauvin-Robinet, Christel / Callier, Patrick / Franco, Brunella / Zuffardi, Orsetta / Payet, Muriel / Aral, Bernard / Gigot, Nadège / Donzel, Anne / Mosca-Boidron, Anne-Laure / Masurel-Paulet, Alice / Huet, Frédéric / Teyssier, Jean-Raymond / Mugneret, Francine / Faivre, Laurence

    American journal of medical genetics. Part A

    2009  Volume 149A, Issue 8, Page(s) 1846–1849

    MeSH term(s) Chromosome Aberrations ; Cohort Studies ; Comparative Genomic Hybridization ; Female ; Genomic Instability ; Humans ; Mutation/genetics ; Orofaciodigital Syndromes/genetics ; Orofaciodigital Syndromes/pathology ; Proteins/genetics
    Chemical Substances OFD1 protein, human ; Proteins
    Language English
    Publishing date 2009-07-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2108614-X
    ISSN 1552-4833 ; 0148-7299 ; 1552-4825
    ISSN (online) 1552-4833
    ISSN 0148-7299 ; 1552-4825
    DOI 10.1002/ajmg.a.32981
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Genomic deletions of OFD1 account for 23% of oral-facial-digital type 1 syndrome after negative DNA sequencing

    Thauvin-Robinet, Christel / Franco, Brunella / Saugier-Veber, Pascale / Aral, Bernard / Gigot, Nadège / Donzel, Anne / Van Maldergem, Lionel / Bieth, Eric / Layet, Valérie / Mathieu, Michèle / Teebi, Ahmad / Lespinasse, James / Callier, Patrick / Mugneret, Francine / Masurel-Paulet, Alice / Gautier, Elodie / Huet, Frédéric / Teyssier, Jean-Raymond / Tosi, Mario /
    Frébourg, Thierry / Faivre, Laurence

    Human mutation. 2009 Feb., v. 30, no. 2

    2009  

    Abstract: Oral-facial-digital type I syndrome (OFDI) is characterised by an X-linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, dental and distal abnormalities, polycystic kidney disease and ... ...

    Abstract Oral-facial-digital type I syndrome (OFDI) is characterised by an X-linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, dental and distal abnormalities, polycystic kidney disease and central nervous system malformations. Considerable allelic heterogeneity has been reported within the OFD1 gene, but DNA bi-directional sequencing of the exons and intron-exon boundaries of the OFD1 gene remains negative in more than 20% of cases. We hypothesized that genomic rearrangements could account for the majority of the remaining undiagnosed cases. Thus, we took advantage of two independent available series of patients with OFDI syndrome and negative DNA bi-directional sequencing of the exons and intron-exon boundaries of the OFD1 gene from two different European labs: 13/36 cases from the French lab; 13/95 from the Italian lab. All patients were screened by a semiquantitative fluorescent multiplex method (QFMPSF) and relative quantification by real-time PCR (qPCR). Six OFD1 genomic deletions (exon 5, exons 1-8, exons 1-14, exons 10-11, exons 13-23 and exon 17) were identified, accounting for 5% of OFDI patients and for 23% of patients with negative mutation screening by DNA sequencing. The association of DNA direct sequencing, QFMPSF and qPCR detects OFD1 alteration in up to 85% of patients with a phenotype suggestive of OFDI syndrome. Given the average percentage of large genomic rearrangements (5%), we suggest that dosage methods should be performed in addition to DNA direct sequencing analysis to exclude the involvement of the OFD1 transcript when there are genetic counselling issues.
    Language English
    Dates of publication 2009-02
    Size p. E320-E329.
    Publishing place Wiley Subscription Services, Inc., A Wiley Company
    Document type Article
    ZDB-ID 1126646-6
    ISSN 1098-1004 ; 1059-7794
    ISSN (online) 1098-1004
    ISSN 1059-7794
    DOI 10.1002/humu.20888
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Genomic deletions of OFD1 account for 23% of oral-facial-digital type 1 syndrome after negative DNA sequencing.

    Thauvin-Robinet, Christel / Franco, Brunella / Saugier-Veber, Pascale / Aral, Bernard / Gigot, Nadège / Donzel, Anne / Van Maldergem, Lionel / Bieth, Eric / Layet, Valérie / Mathieu, Michèle / Teebi, Ahmad / Lespinasse, James / Callier, Patrick / Mugneret, Francine / Masurel-Paulet, Alice / Gautier, Elodie / Huet, Frédéric / Teyssier, Jean-Raymond / Tosi, Mario /
    Frébourg, Thierry / Faivre, Laurence

    Human mutation

    2008  Volume 30, Issue 2, Page(s) E320–9

    Abstract: Oral-facial-digital type I syndrome (OFDI) is characterised by an X-linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, dental and distal abnormalities, polycystic kidney disease and ... ...

    Abstract Oral-facial-digital type I syndrome (OFDI) is characterised by an X-linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, dental and distal abnormalities, polycystic kidney disease and central nervous system malformations. Considerable allelic heterogeneity has been reported within the OFD1 gene, but DNA bi-directional sequencing of the exons and intron-exon boundaries of the OFD1 gene remains negative in more than 20% of cases. We hypothesized that genomic rearrangements could account for the majority of the remaining undiagnosed cases. Thus, we took advantage of two independent available series of patients with OFDI syndrome and negative DNA bi-directional sequencing of the exons and intron-exon boundaries of the OFD1 gene from two different European labs: 13/36 cases from the French lab; 13/95 from the Italian lab. All patients were screened by a semiquantitative fluorescent multiplex method (QFMPSF) and relative quantification by real-time PCR (qPCR). Six OFD1 genomic deletions (exon 5, exons 1-8, exons 1-14, exons 10-11, exons 13-23 and exon 17) were identified, accounting for 5% of OFDI patients and for 23% of patients with negative mutation screening by DNA sequencing. The association of DNA direct sequencing, QFMPSF and qPCR detects OFD1 alteration in up to 85% of patients with a phenotype suggestive of OFDI syndrome. Given the average percentage of large genomic rearrangements (5%), we suggest that dosage methods should be performed in addition to DNA direct sequencing analysis to exclude the involvement of the OFD1 transcript when there are genetic counselling issues.
    MeSH term(s) Female ; Genome, Human/genetics ; Humans ; Orofaciodigital Syndromes/genetics ; Polymerase Chain Reaction ; Proteins/genetics ; Sequence Analysis, DNA ; Sequence Deletion
    Chemical Substances OFD1 protein, human ; Proteins
    Language English
    Publishing date 2008-11-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1126646-6
    ISSN 1098-1004 ; 1059-7794
    ISSN (online) 1098-1004
    ISSN 1059-7794
    DOI 10.1002/humu.20888
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Search for the best indicators for the presence of a VPS13B gene mutation and confirmation of diagnostic criteria in a series of 34 patients genotyped for suspected Cohen syndrome.

    El Chehadeh, Salima / Aral, Bernard / Gigot, Nadège / Thauvin-Robinet, Christel / Donzel, Anne / Delrue, Marie-Ange / Lacombe, Didier / David, Albert / Burglen, Lydie / Philip, Nicole / Moncla, Anne / Cormier-Daire, Valérie / Rio, Marlène / Edery, Patrick / Verloes, Alain / Bonneau, Dominique / Afenjar, Alexandra / Jacquette, Aurélia / Heron, Delphine /
    Sarda, Pierre / Pinson, Lucile / Doray, Bérénice / Vigneron, Jacqueline / Leheup, Bruno / Frances-Guidet, Anne-Marie / Dienne, Gwenaelle / Holder, Muriel / Masurel-Paulet, Alice / Huet, Frédéric / Teyssier, Jean-Raymond / Faivre, Laurence

    Journal of medical genetics

    2010  Volume 47, Issue 8, Page(s) 549–553

    Abstract: Background: Cohen syndrome is a rare autosomal recessive inherited disorder that results from mutations of the VPS13B gene. Clinical features consist of a combination of mental retardation, facial dysmorphism, postnatal microcephaly, truncal obesity, ... ...

    Abstract Background: Cohen syndrome is a rare autosomal recessive inherited disorder that results from mutations of the VPS13B gene. Clinical features consist of a combination of mental retardation, facial dysmorphism, postnatal microcephaly, truncal obesity, slender extremities, joint hyperextensibility, myopia, progressive chorioretinal dystrophy, and intermittent neutropenia.
    Patients and methods: The aim of the study was to determine which of the above clinical features were the best indicators for the presence of VPS13B gene mutations in a series of 34 patients with suspected Cohen syndrome referred for molecular analysis of VPS13B.
    Results: 14 VPS13B gene mutations were identified in 12 patients, and no mutation was found in 22 patients. The presence of chorioretinal dystrophy (92% vs 32%, p=0.0023), intermittent neutropenia (92% vs 5%, p<0.001), and postnatal microcephaly (100% vs 48%, p=0.0045) was significantly higher in the group of patients with a VPS13B gene mutation compared to the group of patients without a mutation. All patients with VPS13B mutations had chorioretinal dystrophy and/or intermittent neutropenia. The Kolehmainen diagnostic criteria provided 100% sensibility and 77% specificity when applied to this series.
    Conclusion: From this study and a review of more than 160 genotyped cases from the literature, it is concluded that, given the large size of the gene, VPS13B screening is not indicated in the absence of chorioretinal dystrophy or neutropenia in patients aged over 5 years. The follow-up of young patients could be a satisfactory alternative unless there are some reproductive issues.
    MeSH term(s) Abnormalities, Multiple/diagnosis ; Abnormalities, Multiple/genetics ; Abnormalities, Multiple/pathology ; Adolescent ; Adult ; Child ; Child, Preschool ; Family ; Female ; Genotype ; Humans ; Male ; Mutation/genetics ; Neutropenia/complications ; Neutropenia/epidemiology ; Neutropenia/genetics ; Reproducibility of Results ; Retinal Diseases/complications ; Retinal Diseases/epidemiology ; Retinal Diseases/genetics ; Retinal Diseases/pathology ; Syndrome ; Vesicular Transport Proteins/genetics ; Young Adult
    Chemical Substances VPS13B protein, human ; Vesicular Transport Proteins
    Language English
    Publishing date 2010-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 220881-7
    ISSN 1468-6244 ; 0022-2593
    ISSN (online) 1468-6244
    ISSN 0022-2593
    DOI 10.1136/jmg.2009.075028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Circulating leukocyte telomere length and oxidative stress: A new target for statin therapy

    Saliques, Sebastien / Teyssier, Jean-Raymond / Vergely, Catherine / Lorgis, Luc / Lorin, Julie / Farnier, Michel / Donzel, Anne / Sicard, Pierre / Berchoud, Juliane / Lagrost, Anne-Cécile / Touzery, Claude / Ragot, Sylviane / Cottin, Yves / Rochette, Luc / Zeller, Marianne

    Atherosclerosis

    Volume v. 219,, Issue no. 2

    Abstract: OBJECTIVES: We investigated the relationship between prior statin therapy and leukocyte telomere length (LTL), as well as their interaction with potential new biomarkers of oxidative deoxyribonucleic acid (DNA) lesions and reactive oxygen species-induced ...

    Abstract OBJECTIVES: We investigated the relationship between prior statin therapy and leukocyte telomere length (LTL), as well as their interaction with potential new biomarkers of oxidative deoxyribonucleic acid (DNA) lesions and reactive oxygen species-induced inflammation. METHODS AND RESULTS: From patients admitted for an acute myocardial infarction, LTL was assessed by quantitative polymerase chain reaction (Q-PCR), and leukocyte Finkel-Biskis-Jinkins osteosarcoma (FOS) and 8-oxoguanine DNA glycosylase (OGG1) messenger ribonucleic acid (mRNA) levels were measured by retrotranscription Q-PCR. Patients under prior chronic statin therapy were compared with patients without statin therapy. Although patients on statin therapy were older, their mean LTL was longer than patients not under statin therapy (1.29±0.11 vs. 1.25±0.11 T/S ratio, p=0.008). In contrast, FOS and OGG1 mRNA levels were similar for the 2 groups. LTL decreased with increasing age, FOS, and OGG1 mRNA levels. Statin therapy remained associated with longer LTL, even after adjustment for confounding factors (p=0.001), and in younger patients (≤64y). Even in groups matched for propensity scores for statin use, LTL was markedly longer in patients under statin therapy. CONCLUSIONS: Our observational study showed that statin therapy was associated with longer LTL. These data bring to light opportunities to identify new targets for early primary preventive treatment strategies. Moreover, our study raised FOS and OGG1 as new relevant biomarkers of LTL.
    Keywords therapeutics ; telomeres ; inflammation ; myocardial infarction ; messenger RNA ; oxygen ; atherosclerosis ; observational studies ; biomarkers ; oxidative stress ; patients ; DNA ; osteosarcoma ; quantitative polymerase chain reaction
    Language English
    Document type Article
    ISSN 0021-9150
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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