ABSTRACT

Purpose

In a cohort of eight families (11 patients) with autosomal recessive retinitis pigmentosa (arRP), we clinically characterized disease associated with mutations in CNGB1.

Methods

Visual function was determined by measuring the patients’ visual acuity, dark- and light-adapted perimetry, and by full-field electroretinography. Retinal structure was evaluated with spectral-domain optical coherence tomography, fundus imaging, and autofluorescence imaging.

Results

Age of onset ranged from 4 to 49 years (mean [SD] 26 [17], median 27 years). The age at visit was 27–54 years, mean 37 (17). The range of visual acuity was logMAR −0.1 to 1.3 (Snellen 20/16 to 20/400) in the right eye and −0.1 to 0.9 (Snellen 20/16 to 20/160) in the left eye. Electrophysiological testing in five patients showed an absence of the rod response. Cone responses ranged from normal to severely reduced. The patients exhibited loss of rod vision more severe than cone vision. Funduscopic images showed widespread retinal degeneration with pigment clumping, optic disk pallor, arteriole attenuation, and a peri-foveal ring of hyper autofluorescence. Three families were tested for olfactory dysfunction and results indicated mild to complete anosmia in individuals with mutations in CNGB1. Genetic analysis revealed 6 novel variants, c.2127 C > G, p.Phe709Leu; c.1431 C > A, p.Cys477*; c.2034 G > A, p.Trp678*; c.2092 T > C, p.Cys698Arg; and c.583 + 2 T > C, c.2305–34 G > A and 3 variants that have been previously described, c.2957A>T, p.Asn986Ile; c.2544dup, p.Leu849Alafs*3; and c.2492 + 1 G > A.

Discussion

This is the first report for six novel CNGB1 variants associated with arRP. Two families had olfactory dysfunction in patients with arRP and family members who were heterozygous for a CNGB1 mutation. Additionally, findings demonstrated variable penetrance and expressivity of disease in these patients.

中文翻译：

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与基因 CNGB1 相关的常染色体隐性视网膜色素变性患者的可变表达

摘要

目的

在一个由 8 个常染色体隐性遗传性色素性视网膜炎 (arRP) 家族（11 名患者）组成的队列中，我们对与CNGB1突变相关的疾病进行了临床表征。

方法

通过测量患者的视力、适应暗光和光的视野以及全视野视网膜电图来确定视觉功能。用光谱域光学相干断层扫描、眼底成像和自体荧光成像评估视网膜结构。

结果

发病年龄为 4 至 49 岁（平均 [SD] 26 [17]，中位数 27 岁）。就诊年龄为 27-54 岁，平均 37 (17) 岁。右眼的视力范围为 logMAR -0.1 至 1.3（Snellen 20/16 至 20/400），左眼的视力范围为 -0.1 至 0.9（Snellen 20/16 至 20/160）。5 名患者的电生理测试显示没有棒状反应。锥体反应范围从正常到严重降低。患者表现出比视锥视力更严重的视杆视力丧失。眼底图像显示广泛的视网膜变性，伴有色素聚集、视盘苍白、小动脉衰减和中心凹周围的高自发荧光环。对三个家庭进行了嗅觉功能障碍测试，结果表明CNGB1突变个体轻度至完全嗅觉丧失. 遗传分析揭示了 6 个新变体，c.2127 C > G，p.Phe709Leu；c.1431 C > A，p.Cys477*；c.2034 G > A，p.Trp678*；c.2092 T > C，p.Cys698Arg；和 c.583 + 2 T > C，c.2305–34 G > A 和 3 个先前描述的变体，c.2957A>T，p.Asn986Ile；c.2544dup，p.Leu849Alafs*3；和 c.2492 + 1 G > A。

讨论

这是与 arRP 相关的六种新型CNGB1变体的第一份报告。arRP 患者和CNGB1突变杂合子的家庭成员中有两个家庭存在嗅觉功能障碍。此外，研究结果表明这些患者的疾病外显率和表现力不同。