Duplication of the TGFBR1 gene causes features of Loeys-Dietz syndrome
Duplication of the TGFBR1 gene causes features of Loeys-Dietz syndrome
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DOI：
10.1016/j.ejmg.2010.08.004
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发表时间：
2010-11-01
影响因子：
1.9
通讯作者：
Devriendt, Koenraad
中科院分区：
文献类型：
--
作者：
Breckpot, Jeroen;Budts, Werner;Devriendt, Koenraad
Loeys-Dietz综合征（LDS; OMIM：609192）是一种常染色体显性遗传疾病，其特征为间距过宽、双悬雍垂或腭裂、动脉迂曲伴广泛的血管动脉瘤和早期主动脉夹层的高风险。LDS是由转化生长因子β受体I和II（TGFBR 1和TGFBR 2）基因突变引起的，改变了亚细胞TGF-β信号的传递，并通过Smad 2的激活增加介导。我们报告了一个17岁的男孩，患有青春期迟缓、双悬雍垂、弯曲趾和面部畸形特征，提示LDS。TGFBR 1和TGFBR 2突变分析正常。通过分子核型分析，检测到两个以前未报道的染色体不平衡：染色体22q13.31q13.32上的120 kb缺失，遗传自未受影响的父母，和染色体9q22.32q31.3上的从头14.6 Mb重复，包含TGFBR 1。我们假设TGFBR 1的拷贝数增加有助于表型。(C)2010年Elsevier Masson SAS。All rights reserved.
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.