Clinical Characterization of CNGB1-Related Autosomal Recessive Retinitis Pigmentosa
Clinical Characterization of CNGB1-Related Autosomal Recessive Retinitis Pigmentosa
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DOI：
10.1001/jamaophthalmol.2016.5213
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发表时间：
2017-02-01
影响因子：
8.1
通讯作者：
Webster, Andrew R.
中科院分区：
文献类型：
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作者：
Hull, Sarah;Attanasio, Marcella;Webster, Andrew R.
重要性视网膜色素变性（RP）与CNGB 1变异体相关的表型的已发表数据有限。这些数据都需要为患者的预后咨询，并了解潜在的治疗windows.Objective描述了详细的临床和分子遗传学研究结果在一系列患者RP可能致病的CNGB1.DESIGN，设置，和参与者在这种情况下，10例患者从9个家庭进行了全面的眼科检查。分子研究包括6例患者的全外显子组分析。研究时间为2013年4月17日至2016年3月3日，末次随访于2016年3月2日结束，数据分析时间为2014年10月27日至2016年3月29日。主要结果与指标眼科检查结果及CNGB 1分子遗传学分析结果。本研究纳入了来自9个家庭的7名女性和3名男性，平均（SD）年龄为47.4（13.2）岁，被确定为具有CNGB 1变体;平均（SD）随访时间为3.7（2.8）年。第一个临床表现是儿童期的夜盲症，后来在平均（SD）33.2（8.0）岁时记录到视野丧失。所有患者的最佳矫正视力均保持至成年期，每只眼的平均值为0.1 logMAR（Snellen当量，20/25）（右眼logMAR范围为0.0至0.3 [Snellen 20/20至20/40]，左眼为-0.1至0.3 [Snellen 20/16至20/40]）。眼底检查发现中周边视网膜色素上皮萎缩及视网膜内色素移行。黄斑的光学相干断层扫描显示，1例患者的内段椭圆带完全保留，其他患者的外侧程度可变，对应于眼底自发荧光增加的旁中心环直径。6例患者的电生理检查证实了视杆-视锥营养不良表型。分子研究确定了一个以前报道的错义变体（p。[N986 I]）和7种以前未在疾病中报道的变体，包括4种无义（p. [(Q88[100]，p. [Q222[100]，p. [Q318*]，和p. [R729*]）、2个移码（p. [A1048fs* 13]，p. [L 849 Afs *3]）和剪接位点变异体（c.761 + 2 T> A）。结论和相关性本研究的数据表明RP患者的视力和中央凹结构在成年后得以保留，因此应该存在一个漫长的机会窗口，用于新疗法的干预。
IMPORTANCE There are limited published data on the phenotype of retinitis pigmentosa (RP) related to CNGB1 variants. These data are needed both for prognostic counseling of patients and for understanding potential treatment windows.OBJECTIVE To describe the detailed clinical and molecular genetic findings in a series of patients with RP with likely pathogenic variants in CNGB1.DESIGN, SETTING, AND PARTICIPANTS In this case series, 10 patients from 9 families underwent full ophthalmologic examination. Molecular investigations included whole-exome analysis in 6 patients. The study was conducted from April 17, 2013, to March 3, 2016, with final follow-up completed on March 2, 2016, and data were analyzed from October 27, 2014, to March 29, 2016.MAIN OUTCOMES AND MEASURES Results of ophthalmologic examination and molecular genetic analysis of CNGB1.RESULTS In this case series, 7 women and 3 men from 9 families with a mean (SD) age of 47.4 (13.2) years identified as having CNGB1 variants were included in this study; there was a mean (SD) follow-up length of 3.7 (2.8) years. The first clinical presentation was with nyctalopia in childhood with visual field loss documented later at a mean (SD) age of 33.2 (8.0) years. All patients had preserved best-corrected visual acuity into adulthood, with a mean of 0.1 logMAR (Snellen equivalent, 20/25) in each eye (logMAR range, 0.0 to 0.3 [Snellen 20/20 to 20/40] in the right eye and -0.1 to 0.3 [Snellen 20/16 to 20/40] in the left eye). Fundus examination revealed midperipheral retinal pigment epithelial atrophy and intraretinal pigment migration. Optical coherence tomography of the macula demonstrated complete preservation of the inner segment ellipsoid band in 1 patient, with variable lateral extent in the other patients corresponding to the diameter of a paracentral ring of increased fundus autofluorescence. Electrophysiologic testing in 6 patients confirmed a rod- cone dystrophy phenotype. Molecular investigations identified a previously reported missense variant (p.[N986I]) and 7 variants not previously reported in disease including 4 nonsense (p.[(Q88*], p.[Q222*], p.[Q318*], and p.[R729*]), 2 frameshift (p.[A1048fs* 13], p.[L849Afs*3]), and a splice site variant (c.761 + 2T > A).CONCLUSIONS AND RELEVANCE The data from this study suggest that visual acuity and foveal structure in patients with RP are preserved into adult life such that a lengthy window of opportunity should exist for intervention with novel therapies.