视网膜色素变性隐性遗传致病基因PDE6B的突变分析  

Screening gene mutations of the β subunit of phosphodiesterase in the Chinese retinitis pigmentosa patients

作　　者：崔云[1] 王立[1] 赵堪兴[1] 王擎 陈薇婴[1] 王犁明[1] 

机构地区：[1]天津市眼科医院眼科研究所 [2]CenterforMolecularGenetics

出　　处：《中华医学遗传学杂志》2003年第3期200-202,共3页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金杰出青年基金 (3982 551 0 )~~

摘　　要：目的　了解常染色体隐性遗传视网膜色素变性 ( autosomal recessive retinitis pigmentosa,ARRP)致病基因磷酸二酯酶 β亚单位 ( phosphodiesteraseβ subunit,PDE6 B)基因在中国视网膜色素变性( retinitis pigmentosa,RP)患者中的突变谱及突变率。方法　应用聚合酶链反应 -单链构象多态性 ,对收集的 35个常染色体隐性 RP家系 38例患者和 5 5例散发 RP患者进行 PDE6 B基因的 2 2个外显子和 5′端非翻译区突变筛选 ;对有变异条带者进行 DNA序列分析。结果　测得一个常染色体隐性家系患者 PDE6 B基因第 11外显子 5′端上游第 19位碱基 (第 10内含子内 )发生 G→ A转换。 1例散发 RP患者同时检测到第 6外显子第 2 4 92位点碱基 T颠换为 C和第 10外显子 5′端上游 (第 9内含子内 )第 2 7～ 2 8碱基之间有两个碱基 TG插入。另两例散发 RP患者分别发现第 4外显子 5′端上游 30～ 31碱基处两个碱基 GT插入和第18外显子 3′端下游第 15个碱基发生 G→C颠换。结论　发现 1名中国人的散发 RP患者携带 RP致病基因 PDE6 B基因的一种复合杂合突变。中国人的 PDE6Objective: To investigate the mutation spectrum of phosphodiesterase β subunit (PDE6B) gene and incidence in Chinese retinitis pigmentosa (RP) patients. Methods: Genomic DNA was extracted from the blood samples of 38 patients from 35 autosomal recessive retinitis pigmentosa (ARRP) families and 55 sporadic cases. The mutation of the PDE6B gene was detected using PCR-SSCP, and the amplified PCR product of abnormal bands was sequenced. Results: Within intron 10 of PDE6B gene, a mutation was found in an ARRP family,a G&rarrA transition at 19th base upstream 5′-end of exon 11. A novel complex heterozygous variant of PDE6B gene in a sporadic case, a T to C transition in codon 323 resulting in the substitution of Gly by Ser and two bp(TG) inserted between the 27th-28th bp upstream of the 5′-end of exon 10 were both present in the same isolate RP. But they were not found in 100 unrelated normal individuals. A sporadic RP was found carrying a sequence variant of PDE6B gene, a G to C transversion in intron 18, the 15th base adjacent to the 3′ end of exon 18. Another isolate RP was found to have 2 bp inserted between 31st and 32nd base upstrem 5′ end of exon 4 (in intron 3) of PDE6B gene. Conclusion: There is a complex heterozygous mutation of PDE6B gene responsible for a sporadic RP patient in China. Several DNA variants were found in intron of PDE6B gene in the national population.

关 键 词：常染色体隐性遗传 视网膜色素变性 致病基因 PDE6B 基因突变 

分 类 号：R774.1[医药卫生—眼科]