The Location And Mutation Screen Of Pathogenic Gene Of Hereditary Lamellar Cataract

Objective: We tried to identify the genetic defect causing Hereditary lamellar Cataract.Methods: 1. To investigate a four-generation Chinese family affected by lamellar cataract in Tianjin, genomic DNA was extracted from peripheral blood leucocytes using standard protocols With informed consent. The affected status was determined before genetic analysis . Determine the pattern of inheritance, exclude the evidence of chromosome defects in karyotype analysis. 2. Three panels of cataract candidate loci were selected for preliminary analysis . Polymerase chain reaction based genotyping of microsatellite markers was done on a automated sequencer. The marker order and intermarker distances were obtained from NCBI. Linkage analysis was carried out by LINKAGE5.2 3. Identify the potential mutation by sequencing the candidate gene.Results: This family shows an autosomal dominant pattern of inheritance by the analysis. There was no evidence of defects in karyotype analysis. By Candidate gene mapping, the maximum lod score (1.63 at recombination fraction theta=0) was obtained for marker d13s1236. The locus linked with the cataract of this family was mapped to 13q11 — 13ql2 and 6.99cM interval between D13S1316 and D13S232. The candidate gene is GJA3. Sequencing of the coding region of GJA3 gene showed a heterozygous transversion G—C in exon.Conclusion: A novel heterozygous mutation in the GJA3 gene which encodeCx46 lead to the lamellar cataract of this Chinese family.