Tuberin
Das TSC2-Gen kodiert eine Protein welches in der Regulation der Zellproliferation beteiligt ist. Mutationen führen zu verschiedenen Erkrankungen mit exzessivem Zellwachstum und benignen Tumoren. Folgende Erkrankungen können abgegrenzt werden: Tuberöse Sklerose 1, Lymphangioleiomyomatose und Isolierte fokale kortikale Dysplasie 2.
Gentests:
Klinisch |
Untersuchungsmethoden |
Familienuntersuchung |
Bearbeitungszeit |
5 Tage |
Probentyp |
genomische DNS |
Verknüpfte Erkrankungen:
Referenzen:
1. |
Sato T et al. (2002) Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis.
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2. |
None (1954) Familial renal adenomas in Wistar rats; a preliminary report.
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3. |
Zhang Y et al. (2003) Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins.
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4. |
Stocker H et al. (2003) Rheb is an essential regulator of S6K in controlling cell growth in Drosophila.
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5. |
Martin N et al. (2003) Discordant clinical manifestations in monozygotic twins with the identical mutation in the TSC2 gene.
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6. |
Shumway SD et al. (2003) 14-3-3beta binds to and negatively regulates the tuberous sclerosis complex 2 (TSC2) tumor suppressor gene product, tuberin.
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7. |
Momose S et al. (2002) Identification of the coding sequences responsible for Tsc2-mediated tumor suppression using a transgenic rat system.
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8. |
Karbowniczek M et al. (2003) Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism.
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9. |
Potter CJ et al. (2002) Akt regulates growth by directly phosphorylating Tsc2.
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10. |
Inoki K et al. (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling.
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11. |
Manning BD et al. (2002) Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway.
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12. |
Langkau N et al. (2002) TSC1 and TSC2 mutations in tuberous sclerosis, the associated phenotypes and a model to explain observed TSC1/ TSC2 frequency ratios.
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13. |
Inoki K et al. (2003) TSC2 mediates cellular energy response to control cell growth and survival.
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14. |
Hodges AK et al. (2001) Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin.
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15. |
Nellist M et al. (2001) TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex.
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16. |
Niida Y et al. (2001) Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions.
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17. |
Khare L et al. (2001) A novel missense mutation in the GTPase activating protein homology region of TSC2 in two large families with tuberous sclerosis complex.
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18. |
Potter CJ et al. (2001) Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size.
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19. |
Tapon N et al. (2001) The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation.
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20. |
Kleymenova E et al. (2001) Tuberin-dependent membrane localization of polycystin-1: a functional link between polycystic kidney disease and the TSC2 tumor suppressor gene.
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21. |
Dabora SL et al. (2001) Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.
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22. |
Cheadle JP et al. (2000) Molecular genetic advances in tuberous sclerosis.
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23. |
Carsillo T et al. (2000) Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis.
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24. |
Way SW et al. (2009) Loss of Tsc2 in radial glia models the brain pathology of tuberous sclerosis complex in the mouse.
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25. |
Ranek MJ et al. (2019) PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress.
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26. |
Du H et al. (2018) A novel mouse model of hemangiopericytoma due to loss of Tsc2.
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27. |
Lim JS et al. (2017) Somatic Mutations in TSC1 and TSC2 Cause Focal Cortical Dysplasia.
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28. |
Ercan E et al. (2017) Neuronal CTGF/CCN2 negatively regulates myelination in a mouse model of tuberous sclerosis complex.
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29. |
Zhang Y et al. (2014) Coordinated regulation of protein synthesis and degradation by mTORC1.
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30. |
Ha JY et al. (2014) Tnfaip8 l1/Oxi-β binds to FBXW5, increasing autophagy through activation of TSC2 in a Parkinson's disease model.
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31. |
Auerbach BD et al. (2011) Mutations causing syndromic autism define an axis of synaptic pathophysiology.
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32. |
Cao J et al. (2010) Thoracic aortic disease in tuberous sclerosis complex: molecular pathogenesis and potential therapies in Tsc2+/- mice.
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33. |
Pollizzi K et al. (2009) A hypomorphic allele of Tsc2 highlights the role of TSC1/TSC2 in signaling to AKT and models mild human TSC2 alleles.
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34. |
Bonnet CS et al. (2009) Defects in cell polarity underlie TSC and ADPKD-associated cystogenesis.
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35. |
Le Caignec C et al. (2009) Three independent mutations in the TSC2 gene in a family with tuberous sclerosis.
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36. |
Astrinidis A et al. (2000) Mutational analysis of the tuberous sclerosis gene TSC2 in patients with pulmonary lymphangioleiomyomatosis.
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37. |
Hartman TR et al. (2009) The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway.
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38. |
Choi YJ et al. (2008) Tuberous sclerosis complex proteins control axon formation.
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39. |
Ehninger D et al. (2008) Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis.
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40. |
Hu J et al. (2008) WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase.
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41. |
Ozcan U et al. (2008) Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis.
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42. |
Au KS et al. (2007) Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States.
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43. |
Jansen AC et al. (2006) Unusually mild tuberous sclerosis phenotype is associated with TSC2 R905Q mutation.
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44. |
Crino PB et al. (2006) The tuberous sclerosis complex.
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45. |
Inoki K et al. (2006) TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth.
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46. |
Nellist M et al. (2005) Distinct effects of single amino-acid changes to tuberin on the function of the tuberin-hamartin complex.
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47. |
Brook-Carter PT et al. (1994) Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease--a contiguous gene syndrome.
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48. |
Sepp T et al. (1996) Loss of heterozygosity in tuberous sclerosis hamartomas.
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49. |
Bjornsson J et al. (1996) Tuberous sclerosis-associated renal cell carcinoma. Clinical, pathological, and genetic features.
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50. |
Vrtel R et al. (1996) Identification of a nonsense mutation at the 5' end of the TSC2 gene in a family with a presumptive diagnosis of tuberous sclerosis complex.
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51. |
Wilson PJ et al. (1996) Novel mutations detected in the TSC2 gene from both sporadic and familial TSC patients.
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52. |
Carbonara C et al. (1996) Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas.
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53. |
Henske EP et al. (1996) Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions.
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54. |
Kumar A et al. (1995) Mutation analysis of the TSC2 gene in an African-American family.
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55. |
Green AJ et al. (1996) Clonality of tuberous sclerosis harmatomas shown by non-random X-chromosome inactivation.
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56. |
None (1993) Identification and characterization of the tuberous sclerosis gene on chromosome 16.
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57. |
Green AJ et al. (1994) Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients.
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58. |
Yeung RS et al. (1994) Predisposition to renal carcinoma in the Eker rat is determined by germ-line mutation of the tuberous sclerosis 2 (TSC2) gene.
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59. |
Sandford R et al. (1996) The tuberin (TSC2), autosomal dominant polycystic kidney disease (PKD1), and somatostatin type V receptor (SSTR5) genes form a synteny group in the Fugu genome.
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60. |
Verhoef S et al. (1995) Somatic mosaicism and clinical variation in tuberous sclerosis complex.
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61. |
Castro M et al. (1995) Pulmonary tuberous sclerosis.
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62. |
Kobayashi T et al. (1995) A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer.
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63. |
Kobayashi T et al. (1995) cDNA structure, alternative splicing and exon-intron organization of the predisposing tuberous sclerosis (Tsc2) gene of the Eker rat model.
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64. |
Wienecke R et al. (1995) Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity.
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65. |
Pilz A et al. (1995) The mouse homologue of the human tuberous sclerosis 2 (TSC2) gene maps to chromosome 17, but does not fall within the tw18 or th20 deletions.
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66. |
Kumar A et al. (1995) A de novo frame-shift mutation in the tuberin gene.
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67. |
Xu L et al. (1995) Alternative splicing of the tuberous sclerosis 2 (TSC2) gene in human and mouse tissues.
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68. |
None (1971) Mutation and cancer: statistical study of retinoblastoma.
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69. |
Webb DW et al. (1991) Non-penetrance in tuberous sclerosis.
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70. |
Imai K et al. (1998) Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes.
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71. |
Yamashita Y et al. (2000) Analysis of all exons of TSC1 and TSC2 genes for germline mutations in Japanese patients with tuberous sclerosis: report of 10 mutations.
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72. |
Au KS et al. (1999) Complete inactivation of the TSC2 gene leads to formation of hamartomas.
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73. |
Niida Y et al. (1999) Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis.
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74. |
Urban T et al. (1999) Pulmonary lymphangioleiomyomatosis. A study of 69 patients. Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P).
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75. |
Verhoef S et al. (1999) Malignant pancreatic tumour within the spectrum of tuberous sclerosis complex in childhood.
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76. |
Jones AC et al. (1999) Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis.
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77. |
Zhang H et al. (1999) Novel TSC2 mutation in a patient with pulmonary tuberous sclerosis: lack of loss of heterozygosity in a lung cyst.
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78. |
Ito N et al. (1999) gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle.
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79. |
Roach ES et al. (1998) Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria.
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80. |
Rennebeck G et al. (1998) Loss of function of the tuberous sclerosis 2 tumor suppressor gene results in embryonic lethality characterized by disrupted neuroepithelial growth and development.
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81. |
Kandt RS et al. (1992) Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease.
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82. |
Beauchamp RL et al. (1998) Exon scanning of the entire TSC2 gene for germline mutations in 40 unrelated patients with tuberous sclerosis.
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83. |
Smolarek TA et al. (1998) Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis.
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84. |
Au KS et al. (1998) Germ-line mutational analysis of the TSC2 gene in 90 tuberous-sclerosis patients.
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85. |
Sampson JR et al. (1997) Renal cystic disease in tuberous sclerosis: role of the polycystic kidney disease 1 gene.
|
86. |
Yates JR et al. (1997) Female germline mosaicism in tuberous sclerosis confirmed by molecular genetic analysis.
|
87. |
Jones AC et al. (1997) Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis.
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88. |
Maheshwar MM et al. (1997) The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis.
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89. |
van Bakel I et al. (1997) Mutations in the TSC2 gene: analysis of the complete coding sequence using the protein truncation test (PTT).
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90. |
Xiao GH et al. (1997) The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis.
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91. |
Au KS et al. (1997) Mutations and polymorphisms in the tuberous sclerosis complex gene on chromosome 16.
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Update: 14. August 2020