Clinical And Molecular Genetic Study Of Three Chinese Families With Retinitis Pigmentosa

Objective The purpose of this research is to study the clinical manifestations of three retinitis pigmentosa families(RP-01, RP-02 and RP-03) and investigate their genetic pathogenesis. RP2 and RPGR gene were screened for the two X-linked retinitis pigmentosa families(RP-01 and RP-02), and for family RP-03, the whole exome sequencing were performed.Methods 1、 Clinical research: After the informed content, the medical history was inquired and the clinical examinations were performed, including the vision acuity, refractive error, slit-lamp, fundus ophthalmoscopy, electroretinogram,VEP and perimetry ex al.2、 Genetic study: 5 ml blood was extracted from patients’ vein vessel. Human genomic DNA was than extracted from peripheral blood leukocytes following the standard procedure provided by the Roche company of America. RP2 and RPGR gene were investigated for all the patients in both RP-01 and RP-02 family. All exons were amplified and sequenced from both directions. The RP-03 family was sent out for the whole exome sequencing. The most possible disease-caused genes were than sequenced by Sanger method.Results 1、RP-01 family was a three generation family including 16 family members, among which 7 were patients, including 3 male patients and 4 female patients. After analyzing the RPGR gene, we found an insertion mutation of c.2002 dup C in exon ORF15 of RPGR gene. It may produce a truncated protein. 100 unaffected individuals were screed to exclude the mutation as a polymorphism in a reference population.2、RP-02 was a four generation family including 14 family members, among which 5 were patients, including 2 male patients and 3 female patients. All patients in this family carried a deletion mutation of c.2899 del G in exon ORF15 of RPGR gene, which may produce a truncated protein. 100 unaffected individuals were screed to exclude the mutation as a polymorphism in a reference population.3、RP-03 was a three generation family including 29 family members, among which 5 were patients and all of them were female patients. After the whole exome sequencing, a stop gain mutation of c. 2371A>T in exon 2 of TOPORS gene was found. The mutation may lead to a truncated protein. 100 unaffected individuals were screed to exclude the mutation as a polymorphism in a reference population.Conclusion 1、The disease-caused mutation in the X linked retinitis pigmentosa family RP-01 was c.2002 dup C in exon ORF15 of RPGR gene; The disease-caused mutation in the X linked retinitis pigmentosa family RP-02 was c.2899 del G in exon ORF15 of RPGR gene too;The disease-caused mutation in the autosomal dominant retinitis pigmentosa family RP-03 was c. 2371A>T in exon of TOPORS gene.2、We found three novel mutations in three different RP families respectively.