Linkage Mapping Of The Two Chinese Family With Autosomal Dominant Retinitis Pigmentosa

Linkage Mapping Of the Two Chinese Family With Autosomal Dominant Retinitis PigmentosaPurpose Retinitis pigmentosa(RP) is a group of progressive retinal diseases characterized by photoreceptor cell degeneration, which eventually leads to blindness. The disease can be inherited in autosomal dominant (adRP), autosomal recessive(arRP) and X-linked(xlRP) patterns. Thirteen loci for autosomal dominant form of RP have been identified , and 12 genes have been cloned from these loci. The purpose of this study is to elucidate the genetic basis of two Chinese family with adRP and to analysis the clinical feature of the patients in these families. Methods Two Chinese families with adRP( WN, and CY) were collected for this study A detailed clinical examination including Humphrey threshold perimetry, and mutifocal electroretinogram(mERG) was performed for all patients in these families The genomic DNA of all family members were extracted from peripheral blood leukocyyes, according to the standard methods of protocal. Polymorphic markers were selected from the regions which harbor all known loci linked with adRP The markers were amplified by polymerase chain reaction(PCR) Fragments were separated by elecrophoresis through 6% denaturing polyacrylamide gels Haplotypes were constructed manually according to the pattern of the bands on the gels stained by silver. Two-point lod scores were calculated using the subroutine Mlink of the Linkage package Mutation analysis of PRKCG, CRX, PRPF31 genes in CY family were performed by screening all coding region of these genes. To determine the contribution of mutation in the genes RHO, NRL and three pre-mRNA splicing-factor genes HPRP3 , PRPC8 and PRPF31 in WN family, the complete coding region of the RHO and NRL, and hotspot regions of mutation in HPRP3, PRPC8 and PRPF31 genes were screened by direct sequencingResults The lod score of each selected marker vs adRP in WN family was negative Two polymorphic change were found in untranslated region(UTR) of RHO One A/G heterzygote was detected at position 70 , and another A/C heterzygote at position 1185. No mutation were found in the coding region of genes RHO and NRL, and also in exon 11 of HPRP3, exon 42 of PRPC8 and exons 5,6,7,8,1 land 14 of PRPF31 genes in WN family. The maximum lod score of 1.33 was acquired between D19S571 and adRP in CY family. A number of non-disease-causing polymorphism were found in CRX, PRKCG and PRPF31 genes in CY family The deletion of four base CACA were detected in intron6 of PRPF31 gene in all patients of CY familyConclusion All known candidate genes associated with adRP were excluded from WN family, and a new disease-causing locus maybe exist in this family. The diseasegene in CY family appear to be linked with 19q 13.4...