Duplication of the TGFBR1 gene causes features of Loeys-Dietz syndrome

被引：13

作者：

Breckpot, Jeroen ^{[1
]}

Budts, Werner ^{[2
]}

De Zegher, Francis ^{[3
]}

Vermeesch, Joris R. ^{[1
]}

Devriendt, Koenraad ^{[1
]}

机构：

[1] Univ Hosp Leuven, Ctr Human Genet, B-3000 Louvain, Belgium

[2] Univ Hosp Leuven, Dept Congenital & Struct Cardiol, B-3000 Louvain, Belgium

[3] Univ Hosp Leuven, Dept Woman & Child, B-3000 Louvain, Belgium

来源：

EUROPEAN JOURNAL OF MEDICAL GENETICS | 2010年 / 53卷 / 06期

关键词：

TGFBR1; Loeys-Dietz syndrome; Array CGH; Bifid uvula; 9q duplication; 22q13; deletion; MARFAN-SYNDROME; MUTATIONS; ANEURYSMS;

D O I：

10.1016/j.ejmg.2010.08.004

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Loeys-Dietz syndrome (LDS; OMIM:609192) is an autosomal dominant disorder characterized by hypertelorism, bifid uvula or cleft palate, and arterial tortuosity with widespread vascular aneurysms and a high risk of aortic dissection at an early age. LDS results from mutations in the transforming growth factor beta-receptor I and II (TGFBR1 and TGFBR2) genes, altering the transmission of the subcellular TGF-beta signal, mediated by increased activation of Smad2. We report on a 17-year-old boy with pubertas tarda, a bifid uvula, camptodactyly and facial dysmorphic features, suggestive of LDS. Mutation analysis of TGFBR1 and TGFBR2 was normal. By means of molecular karyotyping two previously unreported chromosomal imbalances were detected: a 120 kb deletion on chromosome 22q13.31q13.32, inherited from an unaffected parent, and a de novo 14.6 Mb duplication on chromosome 9q22.32q31.3, comprising TGFBR1. We hypothesize that copy number gain of TGFBR1 contributes to the phenotype. (C) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：408 / 410

页数：3

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