An Analysis Of BIGH3 Mutations With Granular Corneal Dystrophy Groenouw Type Ⅰ And Lattice Corneal Dystrophy Type Ⅰ

Granular corneal dystrophy Groenouw type l(CDGGl) and Lattice corneal dystrophy type I (LCD I ) are the most frequent inherited blinding diseases of the cornea. Usually, the first symptoms develop during the second decade as recurrent "attacks" of excruciating corneal erosions and visual impairment due to progressive corneal opacification often leading to corneal transplantation. Histopathologically, CDGG1 displays an accumulation of discrete granular opacities, LCD I is classified as localized amyloidosis. In 1997, Munier and associates isolated a candidate gene from the region of chromosome 5q which was named BIGH3 gene, and they detected mutations in the BIGH3 gene with corneal dystrophy. Thus, it prompts us to study mutations of the BIGH3 gene with corneal dystrophy. This study reports mutations of the BIGH3 gene in two Chinese patients with CDGG1 and in two Chinese patients with LCD I .Objectives:To identify the mutations of BIGH3 in Chinese patients with CDGG1and LCD I . Methods:Genomic DNA was extracted from peripheral blood of the patients which were chosen and 50 normal individuals as controls, and exons 4,11,12,14 of the BIGH3 gene were amplified by polymerase chain reaction(PCR) and then analyzed using the single strand conformational polymorphism(SSCP) technique, the fragments with a mobility shift were direct sequenced to identify the mutations. Some mutations were identified by restriction digestion analysis.Results:A R555W mutation in exon 12 associated with CDGG1 was detected in a family and in a case; a heterozygous mutation of exon 4 in a case with LCD I was discovered which was R124C;a new mutation of T538P was detected in a family with LCD I .Conclusion: 1.BIGH3 gene mutations cause corneal dystrophies.2. Mutations of R124C and R555W of BIGH3 gene were reported in the west and in the east, suggesting these mutations have no difference in races. T538P is a new mutation of BIGH3 gene in a LCDI family.3. Codons R124 and R555 of the BIGH3 gene represent mutational hot spots in patients with CDGG1 and LCD I .4. The useful information is provided from PCR-SSCP and sequencing for making gene diagnosis to corneal dystrophy.