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

Clin Invest Med. 2010 Feb 1;33(1):E14-21. doi: 10.25011/cim.v33i1.11833.

Abstract

Purpose: 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.

MeSH terms

  • Abnormalities, Multiple / genetics
  • Adult
  • Aortic Aneurysm, Thoracic / genetics
  • Asian People / genetics
  • Child
  • China
  • DNA / genetics
  • DNA / isolation & purification
  • DNA Mutational Analysis
  • Female
  • Humans
  • Loeys-Dietz Syndrome / genetics
  • Male
  • Marfan Syndrome / genetics*
  • Mutation*
  • Mutation, Missense
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics*
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / chemistry
  • Receptors, Transforming Growth Factor beta / genetics*

Substances

  • Receptors, Transforming Growth Factor beta
  • DNA
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II