Variants Within TSC2 Exons 25 and 31 are Very Unlikely to Cause Clinically Diagnosable Tuberous Sclerosis (404 views)
Hum Mutat (ISSN: 1059-7794, 1098-1004), 2015 Dec 25; N/D: N/D-N/D.
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Paper type: Journal Article,
Impact factor: 5.089, 5-year impact factor: 4.937
Url: Not available.
Keywords: Alternative Splicing, Diagnosis, Tsc2, Tuberous Sclerosis, Variants,
Affiliations:
*** IBB - CNR ***
Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK., Department of Clinical Genetics, Erasmus MC, 3015CN Rotterdam, The Netherlands., Department of Pediatrics, Division of Neurology, The Children's Hospital of Philadelphia, 502 Abramson Research Center, 3615 Civic Center Blvd, Philadelphia, Pennsylvania, 19104-4318, USA., Department of Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Texas Scottish Rite Hospital for Children, 2222 Welborn Street, Dallas, TX, 75219, USA., University College London Genetics Institute, Darwin building, Gower Street, London, WC1E 6BT, UK., Institute of Structural and Molecular Biology, University College London, London, WC1E 6BT, UK., UF de Genetique Moleculaire, Departement de Biochimie Genetique PBMM, Institut de Biologie en Sante CHU Angers, 4 Rue Larrey, 49933, Angers Cedex 9, France., Centre de Reference des Epilepsies Rares, Hopital Universitaire Necker - Enfants Malades, 149 rue de Sevres, 75743, Paris Cedex 15, France., Neonatology and Neonatal Intensive Care Unit, S. Anna Hospital, Corso Spezia 60, 10126, Torino, Italy., Laboratory of Molecular Genetics, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza, Presidio OIRM S. Anna, Piazza Polonia 94, 10126, Torino, Italy., CNR-IBB UOS-TO at MBC, Molecular Biotechnology Center for University of Turin, Via Nizza 52, 10126, Torino, Italy., Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Institute of Cardiovascular Sciences, University College, London, UK., Department of Medical Sciences, University of Turin, Via Santena 19, 10126, Torino, Italy.,
References:
Not available.
Hum Mutat (ISSN: 1059-7794, 1098-1004), 2015 Dec 25; N/D: N/D-N/D.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 5.089, 5-year impact factor: 4.937
Url: Not available.
Keywords: Alternative Splicing, Diagnosis, Tsc2, Tuberous Sclerosis, Variants,
Affiliations:
*** IBB - CNR ***
Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK., Department of Clinical Genetics, Erasmus MC, 3015CN Rotterdam, The Netherlands., Department of Pediatrics, Division of Neurology, The Children's Hospital of Philadelphia, 502 Abramson Research Center, 3615 Civic Center Blvd, Philadelphia, Pennsylvania, 19104-4318, USA., Department of Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Texas Scottish Rite Hospital for Children, 2222 Welborn Street, Dallas, TX, 75219, USA., University College London Genetics Institute, Darwin building, Gower Street, London, WC1E 6BT, UK., Institute of Structural and Molecular Biology, University College London, London, WC1E 6BT, UK., UF de Genetique Moleculaire, Departement de Biochimie Genetique PBMM, Institut de Biologie en Sante CHU Angers, 4 Rue Larrey, 49933, Angers Cedex 9, France., Centre de Reference des Epilepsies Rares, Hopital Universitaire Necker - Enfants Malades, 149 rue de Sevres, 75743, Paris Cedex 15, France., Neonatology and Neonatal Intensive Care Unit, S. Anna Hospital, Corso Spezia 60, 10126, Torino, Italy., Laboratory of Molecular Genetics, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza, Presidio OIRM S. Anna, Piazza Polonia 94, 10126, Torino, Italy., CNR-IBB UOS-TO at MBC, Molecular Biotechnology Center for University of Turin, Via Nizza 52, 10126, Torino, Italy., Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Institute of Cardiovascular Sciences, University College, London, UK., Department of Medical Sciences, University of Turin, Via Santena 19, 10126, Torino, Italy.,
References:
Not available.
Variants Within TSC2 Exons 25 and 31 are Very Unlikely to Cause Clinically Diagnosable Tuberous Sclerosis
Inactivating mutations in TSC1 and TSC2 cause tuberous sclerosis complex (TSC). The 2012 international consensus meeting on TSC diagnosis and management agreed that the identification of a pathogenic TSC1 or TSC2 variant establishes a diagnosis of TSC, even in the absence of clinical signs. However, exons 25 and 31 of TSC2 are subject to alternative splicing. No variants causing clinically diagnosed TSC have been reported in these exons raising the possibility that such variants would not cause TSC. We present truncating and in-frame variants in exons 25 and 31 in three individuals unlikely to fulfil TSC diagnostic criteria and examine the importance of these exons in TSC using different approaches. Amino acid conservation analysis suggests significantly less conservation in these exons compared to the majority of TSC2 exons, and TSC2 expression data demonstrates that the majority of TSC2 transcripts lack exons 25 and/or 31 in many human adult tissues. In vitro assay of both exons shows that neither exon is essential for TSC complex function. Our evidence suggests that variants in TSC2 exons 25 or 31 are very unlikely to cause classical TSC, although a role for these exons in tissue/stage specific development cannot be excluded. This article is protected by copyright. All rights reserved.
Inactivating mutations in TSC1 and TSC2 cause tuberous sclerosis complex (TSC). The 2012 international consensus meeting on TSC diagnosis and management agreed that the identification of a pathogenic TSC1 or TSC2 variant establishes a diagnosis of TSC, even in the absence of clinical signs. However, exons 25 and 31 of TSC2 are subject to alternative splicing. No variants causing clinically diagnosed TSC have been reported in these exons raising the possibility that such variants would not cause TSC. We present truncating and in-frame variants in exons 25 and 31 in three individuals unlikely to fulfil TSC diagnostic criteria and examine the importance of these exons in TSC using different approaches. Amino acid conservation analysis suggests significantly less conservation in these exons compared to the majority of TSC2 exons, and TSC2 expression data demonstrates that the majority of TSC2 transcripts lack exons 25 and/or 31 in many human adult tissues. In vitro assay of both exons shows that neither exon is essential for TSC complex function. Our evidence suggests that variants in TSC2 exons 25 or 31 are very unlikely to cause classical TSC, although a role for these exons in tissue/stage specific development cannot be excluded. This article is protected by copyright. All rights reserved.
Variants Within TSC2 Exons 25 and 31 are Very Unlikely to Cause Clinically Diagnosable Tuberous Sclerosis
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Variants Within TSC2 Exons 25 and 31 are Very Unlikely to Cause Clinically Diagnosable Tuberous Sclerosis
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Manco M, Ala U, Cantarella D, Tolosano E, Medico E, Altruda F, Fagoonee S
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Impact Factor: 7.135
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Farina AR, Tacconelli A, Cappabianca L, Cea G, Panella S, Chioda A, Romanelli A, Pedone C, Gulino A, Mackay AR
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Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14 (649 views)
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* The RNA-Binding Protein ESRP1 Modulates the Expression of RAC1b in Colorectal Cancer Cells (96 views)
Cancers (ISSN: 2072-6694linking), 2021 Aug 13; 13(16): N/D-N/D.
Impact Factor: 6.126
View Export to BibTeX Export to EndNote
Farina AR, Tacconelli A, Cappabianca L, Cea G, Chioda A, Romanelli A, Pensato S, Pedone C, Gulino A, Mackay AR
* The neuroblastoma tumour-suppressor TrkAI and its oncogenic alternative TrkAIII splice variant exhibit geldanamycin-sensitive interactions with Hsp90 in human neuroblastoma cells (506 views)
Oncogene (ISSN: 1476-5594, 0950-9232), 2009 Nov 19; 28(46): 4075-4094.
Impact Factor: 7.135
View Export to BibTeX Export to EndNote
Farina AR, Tacconelli A, Cappabianca L, Cea G, Panella S, Chioda A, Romanelli A, Pedone C, Gulino A, Mackay AR
* The alternative TrkAIII splice variant targets the centrosome and promotes genetic instability (483 views)
Mol Cell Biol (ISSN: 1098-5549, 0270-7306), 2009 Sep 1; 29(17): 4812-4830.
Impact Factor: 6.057
View Export to BibTeX Export to EndNote
Maglione D, Guerriero V, Viglietto G, Ferraro MG, Aprelikova O, Alitalo K, Del Vecchio S, Lei KJ, Chou JY, Persico MG
Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14 (649 views)
Oncogene (ISSN: 0950-9232, 1476-5594), 1993; 8(4): 925-931.
Impact Factor: 6.772
View Export to BibTeX Export to EndNote
4 Records (4 excluding Abstracts).
Total impact factor: 26.09 (26.09 excluding Abstracts).
Total 5 year impact factor: 19.468 (19.468 excluding Abstracts).
Total impact factor: 26.09 (26.09 excluding Abstracts).
Total 5 year impact factor: 19.468 (19.468 excluding Abstracts).
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