The Gene Mapping And Linkage Analysis For Congenital Fibrosis Of The Extraocular Muscles

Objective Congenital fibrosis of the extraocular muscles (CFEOM) is a kind of syndrom following Mendelian inheritance. In our study,eight short tandem repeat(STR) loci including D12S1048, D12S59, D12D331, D12S345 on chromosome 12 and D16S3026, D16S689, D16S3063, D16S3121 on chromosome 16 were chosen as DNA markers for linkage analysis.Methods The subjects were three CFEOM pedigrees (XT,ZZH and YT) ,25 members in totall,including 15 patients and 10 non-patients.Genomic DNA was extracted from peripheral blood.8 STR genetic markers were analyzed by polymerase chain reaction(PCR). Fragments were separated by electrophoresis through denaturing polyacrylamide gels.Haplotypes were constructed manually according to the pattern of the bands on the gels stained by silver.Linkage analysis was performed by MLINK program from LINKAGE software package(version5.2).Two-point lod score were calculated at recombination rates(0) from 0.000 to 0.400 assuming the male and the female has equal recombination rates.An autosomal domimant model was used withl00%,95%,90% penetrance assuming frequency of disease gene for CFEOM to be 0.000001.According to the lod scores,the linkage relations between STR markers and the gene for CFEOM were judged.Results The results produced by MLINK program were as follows:In pedigree XT,the lod scores for D12 S345,D12S331and D12S1048 were between 1 and 3. The maximum sum two-point lod score of 2.24 for D12S331 was obtained at recombination rates of 0.000 under autosomal dominant model with 100% penetrance. The lod score for D16S3063, D16S689 and D16S3026 were negative at recombination rates between 0.000 and 0.400.In pedigree YT,the lod scores for 8 STR genetic markers were between -1 and 1. In Pedigree ZZH, the lod scores for STR genetic markers were between 0 and 1.Conclusion The disease gene for Pedigree XT may be linked to D12S345,D12S331,D12S1048,but candidate genes in chromosome 16 were excluded. For pedigree YT and ZZH, the disease gene may be consisted with these markers in chromosome 12 and chromosome 16.