Acar Ceren, Mears Alan J, Yashar Beverly M, Maheshwary Anjali S, Andreasson Sten, Baldi Alfonso, Sieving Paul A, Iannaccone Alessandro, Musarella Maria A, Jacobson Samuel G, Swaroop Anand
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
Mol Vis. 2003 Jan 24;9:14-7.
To determine if mutations in the retinal transcription factor gene NRL are associated with retinopathies other than autosomal dominant retinitis pigmentosa (adRP).
Genomic DNA was isolated from blood samples obtained from 50 patients with Leber Congenital Amaurosis (LCA), 17 patients with the Enhanced S-Cone Syndrome (ESCS), and a patient with an atypical retinal degeneration that causes photoreceptor rosettes with blue cone opsin. The 5' upstream region (putative promoter), untranslated exon 1, coding exons 2 and 3, and exon-intron boundaries of the NRL gene were analyzed by direct sequencing of the PCR-amplified products.
Complete sequencing of the NRL gene in DNA samples from this cohort of patients revealed only one nucleotide change. The C->G transversion at nucleotide 711 of NRL exon 3 was detected in one LCA patient; however, this change did not alter the amino acid (L237L).
No potential disease causing mutation was identified in the NRL gene in patients with LCA, ESCS, or the atypical retinal degeneration. Together with previous studies, our results demonstrate that mutations in the NRL gene are not a major cause of retinopathy. To date, only missense changes have been reported in adRP patients, and sequence variations are rare. It is possible that the loss of NRL function in humans is associated with a more complex clinical phenotype due to its expression in pineal gland in addition to rod photoreceptors.
确定视网膜转录因子基因NRL的突变是否与常染色体显性视网膜色素变性（adRP）以外的视网膜病变相关。
从50例莱伯先天性黑矇（LCA）患者、17例增强型S-锥体综合征（ESCS）患者以及1例导致带有蓝色锥体视蛋白的光感受器玫瑰花结的非典型视网膜变性患者的血液样本中分离基因组DNA。通过对PCR扩增产物进行直接测序，分析NRL基因的5'上游区域（假定启动子）、非翻译外显子1、编码外显子2和3以及外显子-内含子边界。
对该组患者DNA样本中的NRL基因进行全序列分析仅发现一个核苷酸变化。在1例LCA患者中检测到NRL外显子3第711位核苷酸的C->G颠换；然而，该变化未改变氨基酸（L237L）。
在LCA、ESCS或非典型视网膜变性患者的NRL基因中未发现潜在的致病突变。与先前的研究一起，我们的结果表明NRL基因的突变不是视网膜病变的主要原因。迄今为止，仅在adRP患者中报道了错义变化，且序列变异很少见。由于NRL除了在视杆光感受器中表达外还在松果体中表达，因此人类中NRL功能的丧失可能与更复杂的临床表型相关。
