Functional Assessment of Variants in the TSC1 and TSC2 Genes Identified in Individuals with Tuberous Sclerosis Complex

被引：70

作者：

Hoogeveen-Westerveld, Marianne ^{[1
]}

Wentink, Marjolein ^{[1
]}

van den Heuvel, Diana ^{[1
]}

Mozaffari, Melika ^{[1
]}

Ekong, Rosemary ^{[2
]}

Povey, Sue ^{[2
]}

den Dunnen, Johan T. ^{[3
]}

Metcalfe, Kay ^{[4
]}

Vallee, Stephanie ^{[5
]}

Krueger, Stefan ^{[6
]}

Bergoffen, JoAnn ^{[7
]}

Shashi, Vandana ^{[8
]}

Elmslie, Frances ^{[9
]}

Kwiatkowski, David ^{[10
]}

Sampson, Julian ^{[11
]}

Vidales, Concha ^{[12
]}

Dzarir, Jacinta ^{[13
]}

Garcia-Planells, Javier ^{[14
]}

Dies, Kira ^{[15
]}

Maat-Kievit, Anneke ^{[1
]}

van den Ouweland, Ans ^{[1
]}

Halley, Dicky ^{[1
]}

Nellist, Mark ^{[1
]}

机构：

[1] Erasmus MC, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands

[2] UCL, Res Dept Genet Evolut & Environm, London, England

[3] Leiden Univ, Med Ctr, Dept Human & Clin Genet, Leiden, Netherlands

[4] Cent Manchester Univ Hosp NHS Fdn Trust, Dept Med Genet, Manchester, Lancs, England

[5] Dartmouth Hitchcock Med Ctr, Dept Clin Genet, Lebanon, NH 03766 USA

[6] Ctr Human Genet, Dresden, Germany

[7] Kaiser Permanente San Jose Med Ctr, Dept Genet, San Jose, CA USA

[8] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA

[9] St George Hosp, Dept Med Genet, London, England

[10] Brigham & Womens Hosp, Translat Med Div, Boston, MA 02115 USA

[11] Cardiff Univ, Inst Med Genet, Cardiff, S Glam, Wales

[12] Policlin Gipuzka, Dept Mol Genet, San Sebastian, Spain

[13] Prince Wales Hosp, Dept Mol Genet, Randwick, NSW 2031, Australia

[14] Univ Valencia, Inst Med Genom, Valencia, Spain

[15] Childrens Hosp Boston, Dept Neurol, Boston, MA USA

来源：

HUMAN MUTATION | 2011年 / 32卷 / 04期

关键词：

tuberous sclerosis complex; TSC1; TSC2; unclassified variants; MUTATIONAL ANALYSIS; MISSENSE MUTATIONS; HAMARTIN; PHENOTYPE; DISEASE; MTOR;

D O I：

10.1002/humu.21451

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The effects of missense changes and small in-frame deletions and insertions on protein function are not easy to predict, and the identification of such variants in individuals at risk of a genetic disease can complicate genetic counselling. One option is to perform functional tests to assess whether the variants affect protein function. We have used this strategy to characterize variants identified in the TSC1 and TSC2 genes in individuals with, or suspected of having, Tuberous Sclerosis Complex (TSC). Here we present an overview of our functional studies on 45 TSC1 and 107 TSC2 variants. Using a standardized protocol we classified 16 TSC1 variants and 70 TSC2 variants as pathogenic. In addition we identified eight putative splice site mutations (five TSC1 and three TSC2). The remaining 24 TSC1 and 34 TSC2 variants were classified as probably neutral. Hum Mutat 32: 424-435, 2011. (C) 2011 Wiley-Liss, Inc.

引用

页码：424 / 435

页数：12

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