NDLI: Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing

Content Provider	PubMed Central
Author	Tyburczy, Magdalena E. Dies, Kira A. Glass, Jennifer Camposano, Susana Chekaluk, Yvonne Thorner, Aaron R. Lin, Ling Krueger, Darcy Franz, David N. Thiele, Elizabeth A. Sahin, Mustafa Kwiatkowski, David J.
Editor	Korf, Bruce R.
Copyright Year	2015
Abstract	Tuberous sclerosis complex (TSC) is an autosomal dominant tumor suppressor gene syndrome due to germline mutations in either TSC1 or TSC2. 10–15% of TSC individuals have no mutation identified (NMI) after thorough conventional molecular diagnostic assessment. 53 TSC subjects who were NMI were studied using next generation sequencing to search for mutations in these genes. Blood/saliva DNA including parental samples were available from all subjects, and skin tumor biopsy DNA was available from six subjects. We identified mutations in 45 of 53 subjects (85%). Mosaicism was observed in the majority (26 of 45, 58%), and intronic mutations were also unusually common, seen in 18 of 45 subjects (40%). Seventeen (38%) mutations were seen at an allele frequency < 5%, five at an allele frequency < 1%, and two were identified in skin tumor biopsies only, and were not seen at appreciable frequency in blood or saliva DNA. These findings illuminate the extent of mosaicism in TSC, indicate the importance of full gene coverage and next generation sequencing for mutation detection, show that analysis of TSC-related tumors can increase the mutation detection rate, indicate that it is not likely that a third TSC gene exists, and enable provision of genetic counseling to the substantial population of TSC individuals who are currently NMI.
Related Links	http://dx.doi.org/10.1371/journal.pgen.1005637
Starting Page	1005637
File Format	PDF
ISSN	15537404
e-ISSN	15537404
Journal	PLoS Genetics
Issue Number	11
Volume Number	11
Language	English
Publisher	Public Library of Science
Publisher Date	2015-11-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Biology Cancer Research Ecology, Evolution, Behavior and Systematics Genetics (clinical)

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