CNGB3 achromatopsia with progressive loss of residual cone function and impaired rod-mediated function
CNGB3 achromatopsia with progressive loss of residual cone function and impaired rod-mediated function
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DOI：
10.1167/iovs.06-1521
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发表时间：
2007-08-01
影响因子：
4.4
通讯作者：
Sieving, Paul A.
中科院分区：
文献类型：
--
作者：
Khan, Naheed Wali;Wissinger, Bernd;Sieving, Paul A.
目的. CNGB 3编码感光细胞质膜中的环核苷酸门控通道的β亚基。CNGB 3突变引起通道病，导致视锥细胞功能受损，表现为色盲。在一个CNGB 3纯合子突变家系和一个CNGB 3和CNGA 3均突变的无关男性家系中，对3名受影响的姐妹篇和3名携带者的临床生理和表型进行评估。通过DNA测序筛选索引患者的CNGA 3和CNGB 3突变。视力检查包括敏锐度、色觉、戈德曼视野（GVF）、暗适应绝对阈值（DAT）、视网膜电图和眼底检查。三个受影响的姐妹篇是纯合的CNGB 3中的1-bp缺失（c.1148delC），该缺失诱导Thr 383后的移码，而携带者是该突变的杂合。无关男性携带外显子6中的杂合8-bp缺失（c.819_826de18bp），以及外显子11中的杂合碱基替换（c.1208G -> A），其导致Arg 403 Gln交换。所有受累受试者的视力范围为20/200至20/400，GVF中度收缩，DAT正常，视杆细胞b波振幅降低，明视b波和闪烁反应消失。视杆感光器的敏感性和振幅，计算通过拟合杆a-波的模型激活的光转导低于正常平均值。携带者视力轻度下降（20/25-20/40），视杆细胞和视锥细胞ERG正常，色觉正常。受影响的受试者的眼底在中年时表现为黄斑萎缩，而携带者在儿童期表现为周边RPE颗粒，在中年晚期表现为黄斑萎缩。黄斑中心凹萎缩可发生在CNGB 3受影响的受试者中，甚至杂合携带者也可表现出黄斑病变。受影响的受试者的视锥ERG反应几乎消失，但有些人保留残余功能到中年，然后逐渐失去甚至这种残余。在一些CNGB 3受影响的受试者中，杆反应受损。
PURPOSE. CNGB3 encodes the beta-subunits of cyclic nucleotidegated channels in the photoreceptor plasma membrane. CNGB3 mutations cause a channelopathy that results in impaired cone function manifesting achromatopsia. The clinical physiology and phenotype of three affected sisters and three carriers were evaluated in a family with a homozygous CNGB3 mutation and an unrelated male harboring both CNGB3 and CNGA3 mutations.METHODS. Index patients were screened for mutations in CNGA3 and CNGB3 by DNA sequencing. Visual examination included acuity, color vision, Goldmann visual fields (GVF), dark-adapted absolute thresholds (DAT), electroretinography, and fundus photography.RESULTS. The three affected sisters were homozygous for a 1-bp deletion (c.1148delC) in CNGB3 that induces a frame shift after Thr383, whereas the carriers were heterozygous for this mutation. The unrelated male carried a heterozygous 8-bp deletion ( c.819_826de18bp) in exon 6, as well as a heterozygous base substitution (c.1208G -> A) in exon 11 that causes an Arg403Gln exchange. All affected subjects had acuity ranging between 20/200 and 20/400, moderately constricted GVFs, normal DATs, reduced rod b-wave amplitudes, and extinguished photopic b-wave and flicker responses. Rod photoreceptor sensitivity and amplitude, calculated by fitting the rod a-waves by a model of activation of phototransduction were below normal mean. Carriers had mildly decreased acuity (20/25-20/40), normal rod and cone ERGs, and normal color vision. The fundi of the affected subjects showed macular atrophy by middle age, while the carriers showed peripheral RPE granularity in childhood and macular atrophy in late middle age.CONCLUSIONS. Foveomacular atrophy can occur in CNGB3-affected subjects, and even heterozygous carriers can exhibit maculopathy. Cone ERG responses in affected subjects are nearly extinguished, but some retain residual function into middle age and then progressively lose even this remnant. Rod responses are impaired in some CNGB3-affected subjects.