Mutation spectrum and genotype-phenotype relevancy of retinitis pigmentosa among Chinese population

Abstract

Purpose : Retinitis pigmentosa (RP) is one of the most common inherited retina degeneration. The genetics of RP in China has not been well studied as far because of population, religious and geographic differences. We aimed to identify the known and novel mutations of Chinese RP patients in Liaoning Province, and to investigate the correlation between the genotypes and the phenotypes.

Methods : In our study, 40 pedigrees diagnosed as RP were assessed by slit-lamp examination, fundus examination, optical coherence tomography (OCT), fundus fluorescein angiography (FFA), flash electroretinogram (FERG) and multifocal electroretinogram (MFERG). The target capture-NGS technology and sanger sequencing were used to detect and validate pathogenic mutations.

Results : We identified 24 known mutations and 22 novel mutations located on 12 known RP genes. Besides USH2A (autosomal recessive, AR) was proved to be the most frequently detected pathogenic gene of RP in our probands, RPGR（X-linked, XL）and RHO（autosomal dominant, AD）were the other two major genes in our study. For patients with mutations in RPGR, the mean ages of onset were 5-6 years, which were earlier than age-onset of ones with RHO (15-20 years old). Visual impairment was also related with ages. Most of the patients with the two mutations gained no light perception between the age of 50-60. It was remarkable that the FFA results showed wider pigmentosa affected area in patients with RPGR mutation than those with RHO mutation. ERG illustrated that the mean amplitude of a-wave and b-wave of the former was lower than the latter. Inheritance patterns of the cases involved in this study could be grouped into three classes: AD (45.5%), AR (45.5%) and XL (9.0%). Interestingly, ADRP patients in our study were more likely to have nyctalopia and poor vision from an earlier age, while ARRP patients were less likely to have poor vision from an early age but more likely to show progression, with more patients over the age of 35 having marked macular edema.

Conclusions : In our study, we identified several new mutations of RP and discovered the correlation among certain genotypes and phenotypes of RP patients. Our findings help to expand the current understanding of the genotypic-phenotypic spectrum of RP and to document the genetic architecture in Chinese population.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.