Homozygosity Mapping in Patients with Cone-Rod Dystrophy: Novel Mutations and Clinical Characterizations
Homozygosity Mapping in Patients with Cone-Rod Dystrophy: Novel Mutations and Clinical Characterizations
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DOI：
10.1167/iovs.10-5797
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发表时间：
2010-11-01
影响因子：
4.4
通讯作者：
den Hollander, Anneke I.
中科院分区：
文献类型：
--
作者：
Littink, Karin W.;Koenekoop, Robert K.;den Hollander, Anneke I.
目的.目的：确定一组主要为非血缘关系的视锥-视杆细胞营养不良（CRD）患者的遗传缺陷并描述其临床特征。招募了139例确诊为CRD的患者。他们中的90人被筛选出ABCA 4中的已知突变，携带一个或两个突变的人被排除在进一步的研究之外。其余108例进行全基因组纯合性作图。对位于纯合区域内的与常染色体隐性视网膜营养不良相关的已知基因进行突变筛查。检测到突变的患者接受进一步的眼科检查。在8个CRD家族中发现了纯合子序列变异，其中6个是非血缘的。在以下六个基因中检测到变体：ABCA 4、CABP 4、CERKL、EYS、KCNV 2和PROM 1。携带ABCA 4、CERKL和PROM 1突变的患者有典型的CRD症状，但眼底镜、光学相干断层扫描和自体荧光成像显示多种视网膜表现。纯合性定位导致在视网膜营养不良的近亲和非近亲患者中鉴定新的突变。详细的临床表征揭示了各种各样的视网膜外观，范围从几乎正常到广泛的视网膜重塑，视网膜变薄和碎片积聚。尽管所有患者最初都被诊断为CRD，但分子学研究结果导致对携带EYS、CABP 4和KCNV 2突变的患者的诊断进行重新评估。（Invest Ophthalmol维斯科学。2010;51：5943-5951）DOI：10.1167/iovs.10-5797
PURPOSE. To determine the genetic defect and to describe the clinical characteristics in a cohort of mainly nonconsanguineous cone-rod dystrophy (CRD) patients.METHODS. One hundred thirty-nine patients with diagnosed CRD were recruited. Ninety of them were screened for known mutations in ABCA4, and those carrying one or two mutations were excluded from further research. Genome-wide homozygosity mapping was performed in the remaining 108. Known genes associated with autosomal recessive retinal dystrophies located within a homozygous region were screened for mutations. Patients in whom a mutation was detected underwent further ophthalmic examination.RESULTS. Homozygous sequence variants were identified in eight CRD families, six of which were nonconsanguineous. The variants were detected in the following six genes: ABCA4, CABP4, CERKL, EYS, KCNV2, and PROM1. Patients carrying mutations in ABCA4, CERKL, and PROM1 had typical CRD symptoms, but a variety of retinal appearances on funduscopy, optical coherence tomography, and autofluorescence imaging.CONCLUSIONS. Homozygosity mapping led to the identification of new mutations in consanguineous and nonconsanguineous patients with retinal dystrophy. Detailed clinical characterization revealed a variety of retinal appearances, ranging from nearly normal to extensive retinal remodeling, retinal thinning, and debris accumulation. Although CRD was initially diagnosed in all patients, the molecular findings led to a reappraisal of the diagnosis in patients carrying mutations in EYS, CABP4, and KCNV2. (Invest Ophthalmol Vis Sci. 2010;51:5943-5951) DOI:10.1167/iovs.10-5797