Jacobson S G, Cideciyan A V, Huang Y, Hanna D B, Freund C L, Affatigato L M, Carr R E, Zack D J, Stone E M, McInnes R R
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104, USA.
Invest Ophthalmol Vis Sci. 1998 Nov;39(12):2417-26.
To define the phenotypes of retinal degenerations associated with mutations in the gene encoding CRX (cone-rod homeobox), a photoreceptor-specific transcription factor.
Heterozygotes with the E168 [delta1 bp], E168 [delta2 bp], or G217 [delta1 bp] CRXgene mutation were studied clinically, with visual function tests, including rod and cone perimetry and electroretinography (ERG), and with optical coherence tomography (OCT).
Clinical diagnoses included autosomal dominant cone-rod dystrophy in one family (E168 [delta1 bp] mutation) and simplex Leber congenital amaurosis in two families (E168 [delta2 bp], G217 [delta1 bp] mutations). In the family with the E168 [delta1 bp] mutation, two siblings had relatively mild disease expression in the third decade of life. The central retinas of these two patients had profound loss of rod and short wavelength cone function; long/middle wavelength cone thresholds were elevated at fixation, but there were greater paracentral than central abnormalities. Peripheral retinal dysfunction was evident by psychophysics and by maximum amplitude loss for rod- and cone-isolated ERG photoreceptor responses. OCT cross-sectional reflectance images showed decreased central retinal thickness consistent with photoreceptor loss. An additional member of this family (E168 [delta1 bp] mutation) and two other patients (representing E168 [delta2 bp] and G217 [delta1 bp] mutations) had a severe phenotype with retina-wide loss of function and islands of function remaining only in the temporal periphery.
Truncation mutations in CRX are associated with retinopathies that share phenotypic features but vary in disease severity. The disease mechanism could involve abnormal photoreceptor development compounded by a disturbance in the maintenance of photoreceptors in the mature retina.
确定与编码视锥-视杆同源框（CRX）的基因突变相关的视网膜变性的表型，CRX是一种光感受器特异性转录因子。
对携带E168[缺失1个碱基对]、E168[缺失2个碱基对]或G217[缺失1个碱基对]CRX基因突变的杂合子进行临床研究，包括视功能测试，如视杆和视锥视野检查及视网膜电图（ERG），以及光学相干断层扫描（OCT）。
临床诊断包括一个家族中的常染色体显性视锥-视杆营养不良（E168[缺失1个碱基对]突变）和两个家族中的单纯性莱伯先天性黑蒙（E168[缺失2个碱基对]、G217[缺失1个碱基对]突变）。在携带E168[缺失1个碱基对]突变的家族中，两名兄弟姐妹在生命的第三个十年疾病表现相对较轻。这两名患者的中央视网膜视杆和短波长视锥功能严重丧失；固定点处长/中波长视锥阈值升高，但旁中心异常比中心更明显。通过心理物理学和视杆和视锥分离的ERG光感受器反应的最大振幅损失可明显看出周边视网膜功能障碍。OCT横断面反射图像显示中央视网膜厚度降低，与光感受器丧失一致。该家族的另一名成员（E168[缺失1个碱基对]突变）和另外两名患者（分别代表E168[缺失2个碱基对]和G217[缺失1个碱基对]突变）具有严重的表型，全视网膜功能丧失，仅颞侧周边残留功能岛。
CRX的截短突变与具有共同表型特征但疾病严重程度不同的视网膜病变相关。疾病机制可能涉及光感受器发育异常，并伴有成熟视网膜中光感受器维持的紊乱。
