Cell
Volume 75, Issue 7, 31 December 1993, Pages 1305-1315
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Article
Identification and characterization of the tuberous sclerosis gene on chromosome 16

https://doi.org/10.1016/0092-8674(93)90618-ZGet rights and content

Abstract

Tuberous sclerosis (TSC) is an autosomal dominant multisystem disorder with loci assigned to chromosomes 9 and 16. Using pulsed-field gel electrophoresis (PFGE), we identified five TSC-associated deletions at 16p 13.3. These were mapped to a 120 kb region that was cloned in cosmids and from which four genes were isolated. One gene, designated TSC2, was interrupted by all five PFGE deletions, and closer examination revealed several intragenic mutations, including one de novo deletion. In this case, Northern blot analysis identified a shortened transcript, while reduced expression was observed in another TSC family, confirming TSC2 as the chromosome 16 TSC gene. The 5.5 kb TSC2 transcript is widely expressed, and its protein product, tuberin, has a region of homology to the GTPaseactivating protein GAP3.

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  • Cited by (0)

    The European Chromosome 16 Tuberous Sclerosis Consortium is comprised of the following groups:

    Group 1: Mark Nellist,1,2† Bart Janssen,2† Phillip T. Brook-Carter,1 Arjenne L. W. Hesseling-Janssen,2 Magitha M. Maheshwar,1 Senno Verhoef,2 Ans M. W. Van den Ouweland,2 Dick Lindhout,2 Bert Eussen,2 Isabel Cordeiro,3 Heloïsa Santos,3 Dicky J. J. Halley,2 and Julian R. Sampson1‡

    1 Institute of Medical Genetics University of Wales College of Medicine Cardiff CF4 4XN Wales

    2 Department of Clinical Genetics Erasmus University and University Hospital 3015 GE Rotterdam The Netherlands

    3 Genetics Unit Hospital Santa Maria 1699 Lisbon Portugal

    Group 2: Christopher J. Ward, Belén Peral, Sandra Thomas, Jim Hughes, and Peter C. Harris

    Medical Research Council Molecular Haematology Unit Institute of Molecular Medicine John Radcliffe Hospital Oxford OX39DU England

    Group 3: Jeroen H. Roelfsema, Jasper J. Saris, Lia Spruit, Dorien J. M. Peters, Johannes G. Dauwerse, and Martijn H. Breuning

    Institute of Human Genetics Leiden University 2333 AL Leiden The Netherlands

    † These authors contributed equally to the work.

    ‡ Correspondence should be addressed to Julian R. Sampson.

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