Mutations of the TGFBR2 gene in Chinese patients with Marfan-related syndrome.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Cardiothoracic Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan P.R. China.
JinLan
J
Chen
BuYun
B
Li
YiFeng
Y
Yang
JianGuo
J
Hu
TianLi
T
Zhao
YiBo
Y
Gong
ZhiPing
Z
Tan
D000015:Abnormalities, Multiple / Q000235:genetics; D000328:Adult; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002648:Child; D002681:China; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D055947:Loeys-Dietz Syndrome / Q000235:genetics; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics*
D018125:Receptors, Transforming Growth Factor beta; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II