Screen of the IMPDH1 gene among patients with dominant retinitis pigmentosa and clinical features associated with the most common mutation, Asp226Asn
Screen of the IMPDH1 gene among patients with dominant retinitis pigmentosa and clinical features associated with the most common mutation, Asp226Asn
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DOI：
10.1167/iovs.04-1197
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
Dryja, TP
中科院分区：
文献类型：
--
作者：
Wada, Y;Sandberg, MA;Dryja, TP
目的.确定IMPDH 1在常染色体显性视网膜色素变性（RP）患者中的突变频率，描述该基因Asp 226 Asn突变患者的临床特征，并将这些特征与其他RP基因中选择性显性突变患者的特征进行比较。对183例显性RP患者的所有14个编码外显子的编码序列及其相邻侧翼内含子序列进行了测序。评估的临床结果包括视力、屈光不正、用Goldmann视野计测量的视野面积、最终暗适应阈值、全视野视网膜电图（ERG）振幅、白内障和眼底镜骨针色素沉着。在183例无关RP患者中，6例发现Asp 226 Asn突变。1例患者携带新的可能致病的Lys 238 Glu变化。在年龄相似的Asp 226 Asn突变患者中，ERG振幅的变化约为100倍。患者的视杆+视锥0.5 Hz ERG振幅和视锥30 Hz ERG振幅降低相似。对于一定量的剩余视野，携带IMPDH 1的患者的ERG振幅更大（平均0.5 Hz ERG/视野比= 9.5 nV/deg（2））与RP 1突变Arg 677 End患者组相比，（2.8 nV/deg（2））、视紫红质（RHO）突变Pro23 His（5.1 nV/deg（2））或RHO突变Pro347 Leu（1.7 nV/deg（2））。IMPDH 1突变占北美显性RP病例的约2%。最常见的突变，Asp 226 Asn，似乎导致视杆细胞功能的丧失至少与视锥细胞功能一样多。平均而言，患有这种形式RP的患者每单位剩余视觉区域保留的ERG振幅是患有其他三种形式显性RP的患者的两到五倍。
PURPOSE. To determine the frequency of mutations in IMPDH1 among patients with autosomal dominant retinitis pigmentosa ( RP), to characterize the clinical features of patients with the Asp226Asn mutation in this gene, and to compare these features with those found among patients with selected dominant mutations in other RP genes.METHODS. The coding sequence and the adjacent flanking intron sequences of all 14 coding exons were sequenced in 183 unrelated patients with dominant RP. The clinical findings evaluated included visual acuity, refractive error, visual field area measured with the Goldmann perimeter, final dark-adaptation threshold, full-field electroretinogram ( ERG) amplitudes, cataract, and funduscopic bone spicule pigmentation.RESULTS. The mutation Asp226Asn was identified in 6 of the 183 unrelated patients with RP. One patient carried the novel, possibly pathogenic, change Lys238Glu. There was approximately a 100-fold variation in ERG amplitudes among patients of similar age with the Asp226Asn mutation. Patients had similar reductions of rod-plus-cone 0.5-Hz ERG amplitude and cone 30-Hz ERG amplitude. For a given amount of remaining visual field, there was a larger ERG amplitude in IMPDH1-carrying patients ( average 0.5-Hz ERG/visual field ratio = 9.5 nV/deg(2)) compared with groups of patients with the RP1 mutation Arg677End (2.8 nV/deg(2)), the rhodopsin (RHO) mutation Pro23His (5.1 nV/deg(2)), or the RHO mutation Pro347Leu (1.7 nV/deg(2)).CONCLUSIONS. IMPDH1 mutations account for approximately 2% of cases of dominant RP in North America. The most frequent mutation, Asp226Asn, appears to cause at least as much loss of rod function as cone function. Patients with this form of RP retain, on average, two to five times more ERG amplitude per unit of remaining visual area than patients with three other forms of dominant RP.