Frequency and characteristics of retinitis pigmentosa I gene point mutation in patients with retinitis pigmentosa: 101 case analysis

Xiaoli ZHANG; Guanyin YANG; Zhipei PENG; Weiling FU

ABSTRACT

BACKGROUND:

Retinitis pigmentosa(RP) is a group of commonest genetic blindness-inducing eyeground diseases, which have relative great heterogenicity in both heredity and phenotype. Pierce et al discovered a new retinal photoreceptor cell specific gene-RP1 in 1999, and also found in their following research that the mutation of this gene can induce autosomal dominant RP(adRP) . Present RP1 molecular genetic researches mainly concentrate in Caucasians.

OBJECTIVE:

To investigate the mutation frequency, characteristics of RP1gene in Chinese RP patients and its role in RP pathogenesis.

DESIGN:

A comparative study by employing RP patients as subjects and healthy individuals as control.

SETTING:

Gene diagnosis and therapy center in a hospital affiliated to a military medical university of Chinese PLA.

PARTICIPANTS:

Totally 101 RP patients without genetic classification were visited patients of the outpatient Department of Ophthalmology of Hong Kong Prince Wales Hospital and Hong Kong Hospital of Ophthalmology between January 1998 and December 2001, which aged between 10 and 79years old(including 43 male and 58 female cases) with an average age of 40years old. Inclusive criteria Cases who were in accordance with the general national and international standards for RP diagnosis(including funduscope observation and electroretinogram test). Exclusive criteria patients of other retinal pathological changes. A total of 190 healthy adults were selected in control group, which had no RP family history and no RP or other eye diseases in eye examination, for the confirmation of whether the detected variation was the polymorphism of RP1 gene.

METHODS:

Totally 101 cases received conformation sensitive electrophoresis(CSGE) and DNA direct sequencing analyses to detect the point mutation in entire RP1 gene encoding range.MAIN OUTCOME

MEASURES:

Mutation frequency and patterns of RP1gene in Chinese RP patients and its role in RP pathogenesis.

RESULTS:

The mutation detectable rate of RP1 gene in all PR patients was 1/101. Mutation ultimately caused serious truncation in RP1 protein. The phenotype of the disease might be originated from functional deficiency in PR1protein synthesis. In addition, 10 missense mutations were found in our study population, most of which were RP1 gene polymorphism except the unconfirmed pathological significance of M479I.

CONCLUSION:

The deletion of corresponding segments(codon 1052-1933) in RP1 protein would induce RP. Large-scale RP1 genotying is necessary, which also can discover more RP-inducing mutation and RP1 gene polymorphism different from other races simultaneously for further fundamental therapy of RP and thorough improvement of the quality of life of the patients.