Purpose: To identify the gene mutation underlying Avellinocorneal dystrophy in a four-generation Chinese pedigree.
Methods: Patients from the family underwent detailed clinical examination including slit-lamp photography and confocal microscope. Genomic DNA extracted from peripheral leukocytes was amplified using touch-down PCR for genescan. Two-point linkage analysis and haplotyping were performed to map the relevant chromosome region. Candidate gene in this region was sequenced to screen out the disease-causing mutation.
Results: Patients in this pedigree were diagnosed withAvellinocorneal dystrophy. Using linkage analysis, responsible gene was mapped to chromosome 5q31.2 with a maximum LOD score of (Zmax) 3.23 at D5S479 (θmax=0.0). Haplotyping constructed by 11 microstallite markers identified the disease-linked chromosome region below D5S808. Sequencing of known gene in this region, TGFBI, revealed a heterozygous transition (c.418 G>A) in exon 4 resulting in Arg124His (R124H) co-segregated with the disease but nor in the unaffected family members and 50 unrelated controls.
Conclusions: Our study demonstrated a G>A transition cause Arg124His of TGFBI responsible for theAvellinocorneal dystrophy in a Chinese pedigree. This result further supports the importance of TGFBIp in maintaining transparency of cornea. |
