Novel mutations of RPGR in Chinese families with X-linked retinitis pigmentosa

Abstract

BackgroundRP (retinitis pigmentosa) is a group of hereditary retinal degenerative diseases. XLRP is a relatively severe subtype of RP. Thus, it is necessary to identify genes and mutations in patients who present with X-linked retinitis pigmentosa.MethodsGenomic DNA was extracted from peripheral blood. The coding regions and intron-exon boundaries of the retinitis pigmentosa GTPase regulator (RPGR) and RP2 genes were amplified by PCR and then sequenced directly. Ophthalmic examinations were performed to identify affected individuals from two families and to characterize the phenotype of the disease.ResultsMutation screening demonstrated two novel nonsense mutations (c.1541C > G; p.S514X and c.2833G > T; p.E945X) in the RPGR gene. The clinical manifestation of family 1 with mutations in exon 13 was mild. Genotype-phenotype correlation analysis suggested that patients with mutations close to the downstream region of ORF15 in family 2 manifested an early loss of cone function. Family 2 carried a nonsense mutation in ORF15 that appeared to have a semi-dominant pattern of inheritance. All male patients and two female carriers in family 2 manifested pathological myopia (PM), indicating that there may be a distinctive X-linked genotype-phenotype correlation between RP and PM.ConclusionsWe identified two novel mutations of the RPGR gene, which broadens the spectrum of RPGR mutations and the phenotypic spectrum of the disease in Chinese families.

A novel mutation of RPGR in a Chinese family with X-linked retinitis pigmentosa

“…According to previous researches, the mutational hotspot of the RPGR ORF15 has been reported to cause pathological myopia (PM) in Asians almost exclusively [22][23] . Zhang et al [5] even suggested that PM appears may be a distinct phenotype that associated with ORF15 nonsense mutations (c.2833G>T p.E945X). There is a possibility that the rehabilitation of cell In rod and cone system, the amplitude of b wave was frequently and severely reduced, while the amplitude of a wave was not readily apparent.…”

“…Genomic DNA was extracted from peripheral blood leukocytes. Primers were designed from GenBank (OMIM 312610) and adopted the published exon 15 sequence (Table 1) [5] . The reaction mixture was set up with high fidelity Taq polymerase (Invitrogen, USA).…”

“…Commonly, the mode of inheritance of this disease can be autosomal dominant (30%-40%), autosomal recessive (50%-60%) and X-linked manner (5%-15%) [3][4] . So far, more than 80 genes have been identified which are associated with RP, including 3 genes (RPGR, RP2, and OFD1) for X-linked retinitis pigmentosa (XLRP) [5][6] . Among all the related genes of XLRP, mutations account for over 70% in RPGR and approximately 8% to 15% in RP2, respectively [7][8] .…”

Genetic dissection of non-syndromic retinitis pigmentosa

“…Severe symptoms, early age of disease onset, fast progression rate, and early macular degeneration have been observed in cases of RP2 disease. [ 229 233 ] Males are more severely affected in comparison to females and become legally blind in the fourth decade of their lives. [ 233 ]…”

“…[ 229 233 ] Males are more severely affected in comparison to females and become legally blind in the fourth decade of their lives. [ 233 ]…”