Sheng Xunlun, Li Zili, Zhang Xinfang, Wang Jing, Ren Hongwang, Sun Yanbo, Meng Ruihua, Rong Weining, Zhuang Wenjuan
Department of Ophthalmology, People Hospital of Ningxia Hui Autonomous Region, Yinchuan, China.
Mol Vis. 2010 Aug 15;16:1620-8.
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.
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.
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.
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.
在一个患有X连锁隐性视网膜色素变性的大型中国家系中筛查视网膜色素变性GTP酶调节蛋白（RPGR）ORF15的突变，并描述受影响男性和女性携带者的表型。
对77名家庭成员进行眼科检查，以确定受影响个体并描述疾病表型。采用聚合酶链反应（PCR）和直接测序法筛查RPGR基因中的突变。
突变筛查发现一个新的突变ORF15+577_578 delAG，该突变导致开放阅读框移位，致使RPGR蛋白过早截断。在该家系的8名受影响男性个体和14名必然携带者女性中检测到该突变，且发现其与该家系的表型共分离。该突变导致男性受影响个体出现严重的视网膜色素变性（RP）表型，夜盲症和视力的发病年龄存在一定差异，但在无RP表型的女性携带者中为隐性遗传。然而，14名女性携带者的屈光状态为中度至高度近视，屈光不正范围为-5.00 D至-22.00 D。
RPGR ORF15中的这种新突变导致男性出现严重的RP表型，而女性携带者无RP表型。中度至高度近视是该家系女性携带者的一个特殊特征。我们的发现扩展了导致X连锁RP的RPGR突变谱，并扩展了一个中国家系中该疾病的表型谱。这一发现将有助于进一步的遗传咨询和基因诊断。
