title: Novel and known mutations of TGFBI, their genotype-phenotype correlation and structural modeling in 3 Chinese families with lattice corneal dystrophy.
abstract: OBJECTIVE
  To report novel transforming growth factor beta-induced (TGFBI) mutations responsible for lattice corneal dystrophy (LCD), the associated genotype-phenotype correlation, and structural changes in the mutant proteins in three Chinese families.
  
  
  METHODS
  Three unrelated Chinese families were diagnosed as Type I LCD. Mutations in TGFBI were detected by sequencing all of the 17 exons and splice sites of the gene. Phenotype, including corneal erosions, and opacification in the families were compared. Structural changes of the mutant proteins were modeled. One hundred healthy volunteers were recruited as controls for sequence analysis of TGFBI.
  
  
  RESULTS
  Two novel mutations, c.(1702G>C and 1706T>A; p.Arg514Pro and Phe515Leu) in TGFBI were identified in Family 1. Two known hotspot mutations, c. 531C>T (p. Arg124Cys) and c.1876A>G (p.His572Arg), were revealed in Family 2 and Family 3, respectively. Sequence analysis in the 100 healthy control subjects, the unaffected members in Family 1, and evolutionary alignment showed that the novel mutations occurred in the conserved amino acids. Structural modeling revealed changes in the 2nd structure of the mutant proteins, but did not detect gross structural changes. Mutations c.(1702G>C and 1706T>A; p.Arg514Pro and Phe515Leu) and the c. 531C>T (p. Arg124Cys) were present in the corneas with sever opacification.
  
  
  CONCLUSIONS
  The novel mutations c.(1702G>C and 1706T>A; p.Arg514Pro and Phe515Leu), c. 531C>T (p. Arg124Cys), c.1876A>G (p.His572Arg) in TGFBI were responsible for LCD in the 3 families. Mutations c.(1702G>C and 1706T>A) (p.Arg514Pro and Phe515Leu) and the c. 531C>T (p. Arg124Cys) were associated with more severe LCD phenotypes in the families. These results provide more data for molecular diagnosis and prognosis of the disease.
authors.affiliation: Zhongshan Ophthalmic Center and State Key laboratory of ophthalmology, Sun Yat-Sen University, Guangzhou, P.R.China.
authors.forename: Xingwu
authors.initials: X
authors.lastname: Zhong
authors.forename: Suqin
authors.initials: S
authors.lastname: Chen
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016415:Sequence Alignment; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000235:genetics*; D014792:Visual Acuity; D055815:Young Adult; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein