title: Two mutations in the transforming growth factor beta-induced gene associated with familial Lattice corneal dystrophy.
abstract: OBJECTIVE
  To report a phenotypic variant pedigree of lattice corneal dystrophy (LCD) associated with two mutations, R124C and A546D, in the transforming growth factor beta-induced gene (TGFBI).
  
  
  METHODS
  A detailed ocular examination was taken for all participants of a LCD family. Peripheral blood leukocytes from each participant were extracted to obtain the DNA. Polymerase chain reaction (PCR) of all seventeen exons of TGFBI gene was performed. The products were sequenced and analyzed. Histological examination was carried out after a penetrating keratoplasty from the right eye of proband.
  
  
  RESULTS
  Genetic analysis showed that the proband and all 6 affected individuals harbored both a heterozygous CGC to TGC mutation at codon 124 and a heterozygous GCC to GAC mutation at codon 546 of TGFBI. None of the 100 control subjects and unaffected family members was positive for these two mutations. Ocular examination displayed multiple refractile lattice-like opacities in anterior stroma of the central cornea and small granular deposits in the peripheral cornea. The deposits were stained positively with Congo red indicating be amyloid in nature and situated mainly in the anterior and middle stroma.
  
  
  CONCLUSIONS
  We observed a novel LCD family which carried two pathogenic mutations (R124C and A546D) in the TGFBI gene. The phenotypic features were apparently different from those associated with corresponding single mutations. The result reveals that although the definite mutation is the most important genetic cause of the disease, some different modifier alleles may influence the phenotype.
authors.affiliation: Eye Hospital, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Cao
authors.affiliation: First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150001, Heilongjiang Province, China.
authors.forename: Hai-Gang
authors.initials: HG
authors.lastname: Yuan
authors.affiliation: Eye Hospital, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Eye Hospital, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Eye Hospital, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Hu
keywords: corneal dystrophy; mutation; phenotype; transforming growth factor beta-induced gene