Nakano Masakazu, Okumura Naoki, Nakagawa Hiroko, Koizumi Noriko, Ikeda Yoko, Ueno Morio, Yoshii Kengo, Adachi Hiroko, Aleff Ross A, Butz Malinda L, Highsmith W Edward, Tashiro Kei, Wieben Eric D, Kinoshita Shigeru, Baratz Keith H
Department of Genomic Medical Sciences Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan 3Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4865-9. doi: 10.1167/iovs.15-17082.
The purpose of this study was to evaluate the association between the intronic expansion of a trinucleotide repeat (TNR) in the TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Japanese population.
Forty-seven Japanese FECD patients and 96 age-matched controls were recruited. FECD patients and controls were examined by slit-lamp and noncontact specular microscopy. The repeat length was determined by direct sequencing and short tandem repeat assay of PCR-amplified DNA and Southern blotting of unamplified DNA.
A TNR expansion, defined as >50 CTG repeats in the TCF4 gene was identified in 12 of 47 FECD cases (26%) and 0 of 96 controls (0%; P < 0.001). Sensitivity and specificity in this study were 26% and 100%, respectively. The clinical characteristics of FECD patients with TNR expansion were not distinct from those without TNR expansion.
These findings show for the first time in a Japanese population the association of the TNR expansion in TCF4 with FECD. In contrast to Caucasian cohorts in whom the TNR expansion is present in most patients with FECD, a CTG expansion is present in a minority of Japanese subjects, indicating other genetic variants as common causes of phenotypically identical disease in this population.
本研究旨在评估日本人群中TCF4基因三核苷酸重复序列（TNR）内含子扩展与Fuchs内皮性角膜营养不良（FECD）之间的关联。
招募了47名日本FECD患者和96名年龄匹配的对照。通过裂隙灯和非接触式角膜内皮显微镜对FECD患者和对照进行检查。通过对PCR扩增的DNA进行直接测序和短串联重复序列分析以及对未扩增的DNA进行Southern印迹分析来确定重复长度。
在47例FECD病例中有12例（26%）检测到TCF4基因中的TNR扩展，定义为>50个CTG重复，而96名对照中无一例（0%；P<0.001）检测到。本研究中的敏感性和特异性分别为26%和100%。TNR扩展的FECD患者的临床特征与未发生TNR扩展的患者并无明显差异。
这些发现首次在日本人群中表明TCF4基因中的TNR扩展与FECD有关。与大多数FECD患者存在TNR扩展的白种人队列不同，少数日本受试者存在CTG扩展，这表明其他基因变异是该人群中表型相同疾病的常见原因。
