RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa
RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa
复制标题
DOI：
10.1086/379379
复制
发表时间：
2003-11-01
影响因子：
9.8
通讯作者：
Berson, EL
中科院分区：
文献类型：
--
作者：
Sharon, D;Sandberg, MA;Berson, EL
我们确定了x连锁色素性视网膜炎（XLRP）患者RP2和RPGR基因的突变谱，并寻找突变类别与疾病严重程度之间的相关性。我们筛选了187例不相关的男性患者进行突变，其中135例临床诊断为XLRP， 11例可能为XLRP， 30例疑似XLRP， 11例锥杆变性。通过单链构象分析和所有RP2外显子和RPGR外显子1-14、ORF15和15a的测序进行突变筛选。测量每位患者的屈光误差、视力、最终暗适应阈值、视野面积和30 hz视锥电图（ERG）振幅。在187例患者中，我们发现10个RP2突变，其中2个为新突变；80个RPGR突变，其中41个为新突变；66%的RPGR突变发生在ORF15内。在135例既往临床诊断为XLRP的患者中，分别有9例（6.7%）和98例（72.6%）发现RP2和RPGR基因突变，占患者总数的79%。与RPGR突变患者相比，RP2突变患者的平均视力较低，但视野面积、最终暗适应阈值和30 hz ERG振幅相似。在RPGR突变的患者中，ORF15突变的患者比外显子1-14的RPGR突变的患者平均具有更大的视野面积和更大的ERG振幅。在ORF15突变患者中，回归分析显示，随着野生型ORF15氨基酸序列长度的增加，最终的黑暗适应阈值变得更低（即更接近正常），30 hz ERG振幅增加。此外，随着ORF15移码突变后异常氨基酸序列的长度增加，疾病的严重程度也随之增加。
We determined the mutation spectrum of the RP2 and RPGR genes in patients with X-linked retinitis pigmentosa (XLRP) and searched for correlations between categories of mutation and severity of disease. We screened 187 unrelated male patients for mutations, including 135 with a prior clinical diagnosis of XLRP, 11 with probable XLRP, 30 isolate cases suspected of having XLRP, and 11 with cone-rod degeneration. Mutation screening was performed by single-strand conformation analysis and by sequencing of all RP2 exons and RPGR exons 1-14, ORF15, and 15a. The refractive error, visual acuity, final dark-adapted threshold, visual field area, and 30-Hz cone electroretinogram (ERG) amplitude were measured in each patient. Among the 187 patients, we found 10 mutations in RP2, 2 of which are novel, and 80 mutations in RPGR, 41 of which are novel; 66% of the RPGR mutations were within ORF15. Among the 135 with a prior clinical diagnosis of XLRP, mutations in the RP2 and RPGR genes were found in 9 of 135 (6.7%) and 98 of 135 (72.6%), respectively, for a total of 79% of patients. Patients with RP2 mutations had, on average, lower visual acuity but similar visual field area, final dark-adapted threshold, and 30-Hz ERG amplitude compared with those with RPGR mutations. Among patients with RPGR mutations, those with ORF15 mutations had, on average, a significantly larger visual field area and a borderline larger ERG amplitude than did patients with RPGR mutations in exons 1-14. Among patients with ORF15 mutations, regression analyses showed that the final dark-adapted threshold became lower (i.e., closer to normal) and that the 30-Hz ERG amplitude increased as the length of the wild-type ORF15 amino acid sequence increased. Furthermore, as the length of the abnormal amino acid sequence following ORF15 frameshift mutations increased, the severity of disease increased.