一个替换的C G锥cGMP-phosphodiesteraseγ亚基基因中发现一种独特的形式的锥萎缩症。
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皮尔N,高YQ,跳舞,门多萨E, Fishman GA,法伯DB
一个替换的C G锥cGMP-phosphodiesteraseγ亚基基因中发现一种独特的形式的锥萎缩症。
眼科学。2005年1月,112 (1):159 - 66。
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15629837 (在PubMed]
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目的:识别基因负责锥营养不良并确定潜在的功能后果突变。设计:病例对照研究。参与者:二百四十无关的患者诊断为锥萎缩症,遗传性锥体杆体营养不良,黄斑营养不良,黄斑变性,或黄斑变性疾病,95控制个人,2有一种独特的锥萎缩症的家庭无关。方法:240年渊源者的dna序列变异筛查PDE6H基因,编码的抑制性gamma-subunit锥环鸟苷酸(cGMP)磷酸二酯酶(PDE))单链构象多态性电泳。核苷酸替换的影响在一个病人的DNA基因表达效率进行了分析通过体外转录/翻译。主要结果测量:Cone-specific基因变异、眼底、视野和视网膜电流图(ERG)的发现,和蛋白质合成效率。结果:我们发现一个杂合的G C替换的5 '非翻译区(UTR) PDE6H基因的DNA的一种独特的锥萎缩症患者,她的兄弟姐妹和他们的父亲。这种罕见的疾病是非常不同的从其他锥营养不良表现,被描述为“与夜盲症和超常杆反应锥萎缩症”,“与超常暗尔格锥萎缩症”和“超常和延迟杆ERG综合症”。Among the 240 patients that we studied, only 1 proband had the G to C variant. Furthermore, none of the 95 controls used in this study had this nucleotide change. We also determined that the PDE6H variant was not present in another family affected with this particular type of cone dystrophy. Because the 5' UTR of mRNAs plays a critical role in the regulation of protein synthesis, we determined the effect of the G to C change in this process. By use of in vitro transcription/translation experiments, we demonstrated that this substitution could lead to an increase in PDE6H gene expression. CONCLUSIONS: Our results indicate that mutations in the PDE6H gene are not common, because only 1 of 240 patients with cone dystrophy showed a single nucleotide substitution in the 5' UTR of PDE6H mRNA that could be associated with the disease. If the effect of the G to C substitution we observed in vitro also occurs in vivo, it will lead to PDE6H overexpression in the photoreceptors. Excess of PDEgamma may affect normal cone cGMP-PDE function by inhibiting the catalytic PDEalpha,beta activity and lead to pathogenic elevation of cGMP and eventual degeneration of cone photoreceptors.