A novel mutation in retinitis pigmentosa GTPase regulator gene with a distinctive retinitis pigmentosa phenotype in a Chinese family.
OBJECTIVE
To screen the mutation in the retinitis pigmentosa GTPase regulator (RPGR) ORF15 in a large Chinese family with X-linked recessive retinitis pigmentosa and describe the phenotype in affected male and female carriers.


METHODS
Ophthalmic examination was performed on 77 family members to identify affected individuals and to characterize the disease phenotype. PCR and direct sequencing were used for screening mutations in the RPGR gene.


RESULTS
Mutation screening demonstrated a novel mutation ORF15+577_578 delAG, which caused an open reading frameshift and resulted in premature truncation of the RPGR protein. The mutation was detected in eight affected male individuals and 14 obligate female carriers of the family and was found to segregate with the phenotype in this family. The mutation led to a severe retinitis pigmentosa (RP) phenotype in male-affected individuals, with some variability in the age of onset of night blindness and visual acuity, but was recessive in female carriers without an RP phenotype. However, the state associated with the carrier was moderate to high myopia with the refractive error ranging from -5.00 D to 22.00 D in 14 female carriers.


CONCLUSIONS
This novel mutation in RPGR ORF15 causes a serious RP phenotype in males and no RP phenotype in female carriers. Moderate to high myopia was a particular feature for female carriers in this pedigree. Our finding expands the spectrum of RPGR mutations causing X-linked RP and expands phenotypic spectrum of the disease in a Chinese family. This finding will be useful for further genetic consultations and genetic diagnosis.
Sheng
Xunlun
X
Department of Ophthalmology, People Hospital of Ningxia Hui Autonomous Region, Yinchuan, China.
Li
Zili
Z
Zhang
Xinfang
X
Wang
Jing
J
Ren
Hongwang
H
Sun
Yanbo
Y
Meng
Ruihua
R
Rong
Weining
W
Zhuang
Wenjuan
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D005654:Fundus Oculi; D050172:Genes, X-Linked / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
D005136:Eye Proteins; C099929:RPGR protein, human
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