Gene Mapping And Genotype-phenotype Correlation In A Chinese Family With Autosomal Retinitis Pigmentosa

Objective (1)To illuminate pathogenic gene and mutation in a Chinese family with autosomal dominant retinitis pigmentosa (adRP). (2)To delineate and analyse phenotype-genotype correlations in the family with autosomal dominant retinitis pigmentosa.Methods (1) A large Chinese adRP family was collected. The RP patients were taken clinical examinations, including visual acuity, direct funduscopy and humphrey threshold perimetry after informed consent. Some patients also underwent electroretinogram (ERG), Fundus fluorescein angiography (FFA) as well as optical coherence tomographic(OCT) assessment. (2) Venous blood were collected from the adRP family members,and genomic DNA were extracted from the blood. Candidate loci was mapped by genetic linkage analysis performed on the known genetic loci for adRP and then all exons of candidate gene were squenced directly after PCR.Results (1)The five-generation pedigree we collected consisted with autosomal dominant inheritance and composed of 12 affected and 20 unaffected members. The phenotype of the patients with RHO mutation showed serious clinic featuring, early onset and rapid deterioration. The night blindness was found when patients were one or two years old which was ealiest onset that have been reported so far. The RP patients suffered aggravating bone spicule degeneration and restriction of peripheral vision and eventually lose sight around 50 years old. ERG showed that the amplitude of a-wave and b-wave decreased significantly or even became extinct in some cases. (2) The disease-causing gene of the Chinese family with adRP was first mapped to the chromosone 3, RHO region,and a missense RHO mutation (p. P171L) was determined in second exon then.Conclusion (1) A missense mutation of rhodopsin gene, 512C> T (P171L ), is responsible for a Chinese family with adRP. (2) The phenotype of the patients with RHO mutation(p. P171L) showed serious clinic featuring.