Purpose: To characterize a Chinese family with inherited retinitis pigmentosa (RP).
Methods: Linkage studies and haplotype analysis were used for gene mapping, and single-strand conformation polymorphism (SSCP) analysis and direct DNA sequence analysis were used for identifying the responsible mutation.
Results: Pedigree analysis suggests that RP in the Chinese family RP002 is inherited either as an autosomal recessive trait or as an X-linked trait. Linkage analysis of RP002 excluded all known autosomal recessive RP loci. Further analysis with 17 polymorphic markers covering the entire X chromosome localized the RP gene in RP002 between markers GATA175D03 and GATA144D04 on Xp11.4, a region where the RP3 gene (RPGR ) is found. Mutation analysis of the RPGR gene in RP002 revealed a novel 28-bp deletion in exon 7. This deletion resulted in an in-frame stop codon that eliminates the C-terminal two-thirds of the RPGR protein. The 28-bp deletion co-segregated with the disease in the family and was not present in 100 normal Chinese individuals. Female carriers of the deletion were affected with myopia and had ERG abnormalities and mild constriction of visual field.
Conclusions: A novel 28-bp deletion in the RPGR gene identified in an X-linked Chinese RP family causes severe RP in male patients as well as myopia and ERG abnormalities in female carriers. The deletion represents the largest microdeletion identified in RPGR to date, and expands the spectrum of RPGR mutations causing XLRP.