Chen JinLan, Li BuYun, Yang YiFeng, Hu JianGuo, Zhao TianLi, Gong YiBo, Tan ZhiPing
Department of Cardiothoracic Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan P.R. China.
Clin Invest Med. 2010 Feb 1;33(1):E14-21. doi: 10.25011/cim.v33i1.11833.
Transforming growth factor beta receptors II gene (TGFBR2) mutations associated with Marfan syndrome and Marfan-associated disorders have been investigated. However, such studies are limited in China. To obtain more information about TGFBR2 mutations, we analyzed 6 unrelated Chinese patients with Marfan-associated disorders and without ocular manifestation.
The genomic DNA from blood leukocytes of these 6 patients and their relatives was isolated, and the entire coding region of TGFBR2 was amplified using PCR. We determined the sequence of TGFBR2 with the ABI 3100 Genetic Analyzer.
Three mutations were identified in TGFBR2. Two mutations were associated with Loeys-Dietz syndrome (LDS), which were distributed as following: one missense mutation R528C (caused by a 1582C > T substitution) and one polymorphism T315M (a rare SNP). The third mutation was a novel silent mutation associated with MFS2, which was K291K caused by an 873 C > T substitution.
The TGFBR2 gene missense mutations are possibly causative mutations of Loeys-Dietz syndrome. This result suggests an increase in the mutation spectrum of Marfan-related disorders in China and possibly world-wide.
已对与马凡综合征及马凡相关疾病相关的转化生长因子β受体II基因（TGFBR2）突变进行了研究。然而，此类研究在中国较为有限。为获取更多关于TGFBR2突变的信息，我们分析了6例无眼部表现的中国马凡相关疾病患者，这些患者之间无亲缘关系。
提取这6例患者及其亲属外周血白细胞的基因组DNA，采用聚合酶链反应（PCR）扩增TGFBR2的整个编码区。我们使用ABI 3100遗传分析仪测定TGFBR2的序列。
在TGFBR2中鉴定出3个突变。2个突变与洛伊氏综合征（LDS）相关，分布如下：1个错义突变R528C（由1582C>T替换引起）和1个多态性T315M（一种罕见的单核苷酸多态性）。第3个突变是与MFS2相关的一个新的沉默突变，即由873C>T替换导致的K291K。
TGFBR2基因错义突变可能是洛伊氏综合征的致病突变。这一结果表明中国乃至全球马凡相关疾病的突变谱有所增加。
