一个中国视网膜色素变性家系的RP3基因突变

A RP3 gene mutation in a Chinese family with X-linked dominant retinitis pigmentosa

目的探讨一个中国视网膜色素变性(RP)家系的突变基因位点。方法在获得知情同意后对该家系成员进行病史采集、眼部检查和病情追溯,绘制家系图,并对其中26例采血,进行DNA提取、聚合酶链反应、RP3基因外显子ORF15测序。结果该家系共有成员57名,其中直系42名(含21例患者)。患者表现为夜盲、近视、眼底色素沉着、血管细、视盘淡,视野向心性缩窄甚至呈管状,暗视视网膜电图(ERG)显示a波、b波振幅明显下降甚至记录不到。家系特点为男性患者的女儿全部患病、男性患者的母亲均是患者,符合X连锁显性遗传特征。经PCR反向测序,发现突变位点位于ORF15+1339delA。结论该家系患者病变由RP3基因外显子ORF15+1339delA位点突变所致。

Objective To investigate the gene mutation in a Chinese family with retinitis pigmentosa（RP）.Methods After informed consent,the family tree was pictured according to clinical findings and consanguineous or marital relationship.Clinical features were evaluated by medical history,visual acuity,fundus examination,electroretinography record and kinetic visual field testing.The deceased or absent members were retrospected to analyze whether they were affected.The genomic DNA from peripheral blood sample in 26 family members was extracted,purified and amplified by polymerase chain reaction（PCR）.A strategy was taken to directly sequence the repetitive part of RP3 exon ORF15 with nested sequencing primers from the PCR product.Results Twenty-one affected persons were found in 42 consanguineous individuals from overall 57 family members.These affected persons were characterized by night blindness,myopia,vascular attenuation and pigmentation in retina,narrowing or tunnel of visual field and reduced or unrecordable electroretinogram.There were 5 generations in the family with 1-11 affected persons in each generation except the 5th one.The hereditary characteristic in this family presented with all affected daughters and affected mother of male patient except Ⅴ：1,who was only 2 years old,demonstrating a dominant X-linked fashion.Inverse PCR revealed a mutation location in ORF15＋1339delA.Conclusion The mutation of ORF15＋1339delA in RP3 gene results in RP in the family.