Analysis of TSC2 stop codon variants found in tuberous sclerosis patients

Miriam A. Goedbloed; Mark Nellist; Brend Verhaaf; Arnold J.J. Reuser; Dick Lindhout; Lone Sunde; Senno Verhoef; Dicky J.J. Halley; Ans M.W. Van den Ouweland

doi:10.1038/sj.ejhg.5200728

Analysis of TSC2 stop codon variants found in tuberous sclerosis patients

Miriam A. Goedbloed, Mark Nellist, Brend Verhaaf, Arnold J.J. Reuser, Dick Lindhout, Lone Sunde, Senno Verhoef, Dicky J.J. Halley, Ans M.W. Van den Ouweland

Research output: Contribution to journal › Journal article › Research › peer-review

6 Citations (Scopus)

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations to the TSC1 and TSC2 tumour suppressor genes. We detected two sequence changes involving the TSC2 stop codon and investigated the effects of these changes on the expression of tuberin, the TSC2 gene product, and on the binding between tuberin and the TSC1 gene product, hamartin. While elongation of the tuberin open reading frame by 17 amino acids did not interfere with tuberin-hamartin binding, a longer extension prevented this interaction. Our data illustrate how functional protein assays can assist in the verification and characterisation of disease-causing mutations.

Original language	English
Journal	European Journal of Human Genetics
Volume	9
Issue number	11
Pages (from-to)	823-828
Number of pages	6
ISSN	1018-4813
DOIs	https://doi.org/10.1038/sj.ejhg.5200728
Publication status	Published - 2001
Externally published	Yes

Keywords

Hamartin
Stop codon mutations
Tuberin
Tuberous sclerosis

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@article{d606fb4baf9c4196a61047241727821b,

title = "Analysis of TSC2 stop codon variants found in tuberous sclerosis patients",

abstract = "Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations to the TSC1 and TSC2 tumour suppressor genes. We detected two sequence changes involving the TSC2 stop codon and investigated the effects of these changes on the expression of tuberin, the TSC2 gene product, and on the binding between tuberin and the TSC1 gene product, hamartin. While elongation of the tuberin open reading frame by 17 amino acids did not interfere with tuberin-hamartin binding, a longer extension prevented this interaction. Our data illustrate how functional protein assays can assist in the verification and characterisation of disease-causing mutations.",

keywords = "Hamartin, Stop codon mutations, Tuberin, Tuberous sclerosis",

author = "Goedbloed, {Miriam A.} and Mark Nellist and Brend Verhaaf and Reuser, {Arnold J.J.} and Dick Lindhout and Lone Sunde and Senno Verhoef and Halley, {Dicky J.J.} and {Van den Ouweland}, {Ans M.W.}",

note = "Funding Information: The authors would like to thank the TSC families involved in this study, and their attending physicians, for their participation and cooperation, and C Withagen-Hermans for performing the loss of heterozygosity study. Financial support was provided by the Tuberous Sclerosis Alliance (USA), Noortman b.v., Maastricht and the Nationaal Epilepsie Fonds (Netherlands).",

year = "2001",

doi = "10.1038/sj.ejhg.5200728",

language = "English",

volume = "9",

pages = "823--828",

journal = "European Journal of Human Genetics",

issn = "1018-4813",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - Analysis of TSC2 stop codon variants found in tuberous sclerosis patients

AU - Goedbloed, Miriam A.

AU - Nellist, Mark

AU - Verhaaf, Brend

AU - Reuser, Arnold J.J.

AU - Lindhout, Dick

AU - Sunde, Lone

AU - Verhoef, Senno

AU - Halley, Dicky J.J.

AU - Van den Ouweland, Ans M.W.

N1 - Funding Information: The authors would like to thank the TSC families involved in this study, and their attending physicians, for their participation and cooperation, and C Withagen-Hermans for performing the loss of heterozygosity study. Financial support was provided by the Tuberous Sclerosis Alliance (USA), Noortman b.v., Maastricht and the Nationaal Epilepsie Fonds (Netherlands).

PY - 2001

Y1 - 2001

N2 - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations to the TSC1 and TSC2 tumour suppressor genes. We detected two sequence changes involving the TSC2 stop codon and investigated the effects of these changes on the expression of tuberin, the TSC2 gene product, and on the binding between tuberin and the TSC1 gene product, hamartin. While elongation of the tuberin open reading frame by 17 amino acids did not interfere with tuberin-hamartin binding, a longer extension prevented this interaction. Our data illustrate how functional protein assays can assist in the verification and characterisation of disease-causing mutations.

AB - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations to the TSC1 and TSC2 tumour suppressor genes. We detected two sequence changes involving the TSC2 stop codon and investigated the effects of these changes on the expression of tuberin, the TSC2 gene product, and on the binding between tuberin and the TSC1 gene product, hamartin. While elongation of the tuberin open reading frame by 17 amino acids did not interfere with tuberin-hamartin binding, a longer extension prevented this interaction. Our data illustrate how functional protein assays can assist in the verification and characterisation of disease-causing mutations.

KW - Hamartin

KW - Stop codon mutations

KW - Tuberin

KW - Tuberous sclerosis

UR - http://www.scopus.com/inward/record.url?scp=0035663354&partnerID=8YFLogxK

U2 - 10.1038/sj.ejhg.5200728

DO - 10.1038/sj.ejhg.5200728

M3 - Journal article

C2 - 11781698

AN - SCOPUS:0035663354

SN - 1018-4813

VL - 9

SP - 823

EP - 828

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 11

ER -

Analysis of TSC2 stop codon variants found in tuberous sclerosis patients

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Keywords

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