Analysis Of Clinical Features And Study Of Responsible Genes For The Chinese Retinitis Pigmentosa And Usher Syndrome Families

Objective:1. To establish the standard system to collect and preserve the genetic resources of retinitis pigmentosa.2. To analyze the clinical and genetic features of the three retinitis pigmentosa families: RP-GC-001 RP-DX-002 RP-PG-003, and to find pathogenic genes for the families.3. To analyze the clinical features of the two Usher Syndrome families: USH-001 USH-002, and to find possible relevant USH gene map locus.Methods:1. RP patients were identified and classified, and their genetic patterns were analyzed. Collecting and preserving RP genetic resources including signing the informed consent, filling out RP questionnaire, extracting genomic DNA from peripheral blood, identification and preservation genomic DNA. Establishing RP genetic resources system including paper-based records management system and electronic records management system.2. Analysis of the clinical and pedigree features of RP-GC-001 RP-DX-002 RP-PG-003 families. And detecting the 15 exons of the five known pathogenic genes: RHO, RDS, ROM1, NRL and CRX by PCR and direct sequencing.3. Analysis of the clinical and pedigree features of USH-001 USH-002 families. And screening the short tandem repeat markers around the 12 known USH gene map locus to choose the possible relevant genes by use of the principles and methods of linkage analysis.Results:1. The system of collecting and preserving genetic resources of RP was standard scientific and reasonable. And it was in line with the international and domestic requirements and principles of genetic resources collection.2. The common phenotype of the families RP-GC-001 P-PG-002 and RP-DX-003 were night blindness, narrowing of vision, bone cell-like retinal pigmentation, shrink of papilla of optic nerve. The phenotype vertically transmitted and appeared in both male and female patients. However, RP-DX-002 family had some characteristics: bone cell-like retinal pigmentation involved in macular and environment of papilla of optic nerve, many patients were with iris adhesion and soot-like vitreous opacity. And patients in RP-PG-003 family would have acute angle-closure glaucoma in their fifties. RHO exon 2 coding region of 403 C>T Argl35Trp R135W mutation was found in the RP-GC-001 familiy, and no pathogenic mutations of RHO RDS ROM1 CRX and NRL were found in the RP-PG-002 and RP-DX-003 families.3. The phenotypes of the family USH-001 were similar to family USH-002: hearing loss in both ears in childhood, non-progressive sensorineural hearing loss, high-frequency hearing loss and normal vestibular function. Night blindness occurred in 10-13 years old and gradually got worse with age, visual field gradually narrowed to tubular vision, while the decline of visual acuity were not obvious. Their clinical manifestations were consistent with the diagnosis of USH2. The phenotype did not consecutively transmitte and appeared in both male and female patients. And patients in these two families all had normal children. In USH-001 family all the patients shared the same Allele of D11S902 and D17S785 short tandem repeat markers, and all the patients in USH-002 family shared the same Allele of D1S425and D9S1776 markers.Conclusion:1. Establishment of the system to preserve and collect RP genetic resources have ensured this study was standardized and had good continuity. It would make our follow-up results of positional cloning, molecular epidemiological study and genetic screening true and reliable. 2. The three RP families were autosomal dominant RP families. The mutation of RHO exon 2 coding region of 403 C>T Argl35Trp R135W was pathogenic mutation in RP-GC-001 family. RHO, RDS, ROM1, CRX and NRL were not the pathogenic genes for RP-PG-002 family and RP-DX-003 family.3. USH-001 and USH-002 were USH2 families and their genetic forms were autosomal recessive. USHIC and USH1G were likely pathogenic genes for USH-001 family, USH2A and USH2D were likely pathogenic genes for USH-002 family.