Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder displaying a large spectrum of symptoms. Linkage studies have shown two loci, TSC1 in 9q34 and TSC2 in 16p13.3, to be involved in the disease. The TSC2 gene, composed of 41 exons, has been isolated and is shown to encode a protein, tuberin, from a 5.5-kb transcript. Mutation screening for both clinical diagnosis and identification of functional domains within the tuberin is in progress. In this study we identify a 33-bp in-frame deletion (1462de133) in the mRNA which segregates in two unrelated French families with severe TSC phenotypes. The corresponding 11 amino acids deletion (aa 482–492) is shown to result from two different splice site mutations at exon 14 and, when compared with the position of two previously described missense mutations, indicates a novel functionally important region of the protein.
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Acknowledgements
We would like to thank Sylvie Dumas for helpful discussions and critical reading of the manuscript. We would also like to thank Sylvie Larget and Jean-François Prud’homme from Genethon for their help with cell cultures. This work was supported in part by grants from the Centre National de la Recherche Scientifique (CNRS), the Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche (MENESR), the Association Française contre les Myopathies (AFM), the Association pour la Recherche contre le Cancer (ARC) and Rhône-Poulenc Rorer (RPR). S.J. held a fellowship from the CNRS and the ARC. G.P. held a fellowship from the MENESR and the University Paris 7. We would also like to thank the patients, their families and clinicians for making this work possible.
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Jobert, S., Bragado-Nilsson, E., Samolyk, D. et al. Deletion of 11 Amino Acids in Tuberin Associated with Severe Tuberous Sclerosis Phenotypes: Evidence for a New Essential Domain in the First Third of the Protein. Eur J Hum Genet 5, 280–287 (1997). https://doi.org/10.1007/BF03405930
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DOI: https://doi.org/10.1007/BF03405930
