Cone dystrophy with supernormal rod response is strictly associated with mutations in KCNV2
Cone dystrophy with supernormal rod response is strictly associated with mutations in KCNV2
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DOI：
10.1167/iovs.07-0471
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发表时间：
2008-02-01
影响因子：
4.4
通讯作者：
Rosenberg, Thomas
中科院分区：
文献类型：
--
作者：
Wissinger, Bernd;Dangel, Susann;Rosenberg, Thomas
目的.视锥细胞营养不良伴超常视杆细胞反应（CDSRR）是一种视网膜疾病，其特征为视敏度降低、色觉缺陷和ERG反应的特定改变，其特征在于高亮度强度下暗视b波振幅升高。PDE 6 H和KCNV 2中的突变已在CDSRR中描述。在CDSRR患者队列中进行了临床和遗传学联合研究，以证实这些先前的结果。来自13个家庭的17名患者进行了详细的眼科检查，包括色觉测试，戈德曼视野，眼底照相，Ganzfeld和多焦ERG，光学相干断层扫描。PDE 6C和KCNV 2的编码序列和侧翼内含子/UTR序列通过DHPLC和PCR扩增的基因组DNA的直接DNA测序来筛选突变。尽管在PDE 6 H基因中未检测到突变，但在所有患者中均发现KCNV 2突变，无论是纯合状态还是复合杂合状态。11个已鉴定的突变中有10个是新的，包括3个错义突变、6个截短突变和1个总缺失。根据隐性遗传模式，突变在所有可用的家系中一致分离。CDSRR表型与不同程度的视力下降和色觉缺陷有关。9例患者存在黄斑缺陷，从轻度色素改变到明显的中心凹萎缩。7例随访患者中仅3例观察到疾病进展。视锥细胞营养不良与视杆细胞超常反应的表型与KCNV 2的突变密切相关。
PURPOSE. Cone dystrophy with supernormal rod response (CDSRR) is a retinal disorder characterized by reduced visual acuity, color vision defects, and specific alterations of ERG responses that feature elevated scotopic b-wave amplitudes at high luminance intensities. Mutations in PDE6H and in KCNV2 have been described in CDSRR. A combined clinical and genetic study was conducted in a cohort of patients with CDSRR, to substantiate these prior results.METHODS. Seventeen patients from 13 families underwent a detailed ophthalmic examination including color vision testing, Goldmann visual fields, fundus photography, Ganzfeld and multifocal ERGs, and optical coherence tomography. The coding sequences and flanking intron/UTR sequences of PDE6C and KCNV2 were screened for mutations by means of DHPLC and direct DNA sequencing of PCR-amplified genomic DNA.RESULTS. Whereas no mutations were detected in the PDE6H gene, mutations in KCNV2 were identified in all patients, in either the homozygous or compound heterozygous state. Ten of the 11 identified mutations were novel, including three missense and six truncating mutations and one gross deletion. The mutations concordantly segregate in all available families according a recessive mode of inheritance. The CDSRR phenotype was associated with reduced visual acuity of variable degree and color vision defects. Macular defects ranging from mild pigmentary changes to distinct foveal atrophy were present in nine patients. Progression of the disease was observed in only three of seven patients with follow-up data.CONCLUSIONS. The phenotype of cone dystrophy with supernormal rod response is tightly linked with mutations in KCNV2.