title: An Arg124His mutation in TGFBI associated to Avellino corneal dystrophy in a Chinese pedigree.
abstract: OBJECTIVE
  To identify the gene mutation underlying Avellino corneal dystrophy in a four-generation Chinese pedigree.
  
  
  METHODS
  Patients from the affected family underwent detailed clinical examination involving slit-lamp photography and confocal microscopy. Genomic DNA extracted from peripheral leukocytes was amplified using touch-down PCR for gene scanning. Two-point linkage analysis and haplotyping were performed to map the relevant chromosome region. The candidate gene in this region was sequenced to screen out the disease-causing mutation.
  
  
  RESULTS
  Patients in the pedigree were diagnosed with Avellino corneal dystrophy. Using linkage analysis, the responsible gene was mapped to chromosome 5q31.2 with a maximum LOD (log odds) score (Z(max)) of 3.23 at D5S479 (θ(max)=0.0). Haplotypes constructed from 11 microstallite markers identified the disease-linked chromosome region as being below D5S808. Sequencing of TGFBI (transforming growth factor-beta induced gene), a known gene in this region, revealed a heterozygous transition (c.418 G>A) in exon 4 resulting in Arg124His (R124H) being co-segregated with the disease in affected family members but not in the unaffected members or the 50 unrelated controls.
  
  
  CONCLUSIONS
  Our study demonstrated that a G>A transition in Arg124His of TGFBI was responsible for Avellino corneal dystrophy in a Chinese pedigree. This result further supports the importance of TGFBIp in maintaining transparency of the cornea.
authors.affiliation: Department of Ophthalmology, Xinhua Hospital, Medical College of Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Gu
authors.forename: Peiquan
authors.initials: P
authors.lastname: Zhao
authors.forename: Guang
authors.initials: G
authors.lastname: He
authors.forename: Chunling
authors.initials: C
authors.lastname: Wan
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Guoyin
authors.initials: G
authors.lastname: Feng
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Linghan
authors.initials: L
authors.lastname: Gao
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein