Objectives: The objective of this study is to investigate the molecular mechanisms and genotype-phenotype correlations of a Chinese family with X-linked retinitis pigmentosa (XLRP).
Methods: A four-generation family with a total of 41 individuals including 7 affected males was recruited. All subjects in this pedigree underwent a complete ophthalmic examination. Targeted capture and next-generation sequencing were performed on the proband using a multigene panel containing 57 known causative genes of retinitis pigmentosa (RP), including RP1, RP2, RPGR, RHO, PRPH2, CRB1 among others. All variants were verified in the remaining family members by polymerase chain reaction amplification and Sanger sequencing. Blood DNA was used for X-chromosome inactivation analysis in female carriers.
Results: All the affected individuals were diagnosed with RP. The affected males showed symptoms from the first decade, while the female carriers had onset in the second decade or later. A frameshift mutation c.345_348delTGAA in the RPGR gene was identified in all affected males and female carriers. By XCI analysis, we found that there was little correlation between their phenotype and the methylation status of their X chromosomes.
Conclusions: A novel mutation c.345_348delTGAA of the RPGR gene was identified, expanding the spectrum of RPGR mutations causing XLRP. In this pedigree, the phenotype extended to female carriers, in whom RP was milder and its onset delayed compared to hemizygous males. Although lack of strong correlation between X-inactivation and the severity of the disease, the milder, variable effects in female carriers still could reflect X-inactivation patterns in the retina of each individual.