Hou Yu-Chih, Wang I-Jong, Hsiao Cheng-Hsiang, Chen Wei-Li, Hu Fung-Rong
Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Mol Vis. 2012;18:362-71. Epub 2012 Feb 7.
To determine the phenotype-genotype correlations in patients with corneal dystrophies associated with human transforming growth factor-β-induced (TGFBI) mutations at the National Taiwan University Hospital.
Twenty-five affected patients from 15 families with corneal dystrophies were recruited. They underwent slit-lamp biomicroscopy and visual acuity examinations. Genomic DNA was extracted from their peripheral blood, and the exons amplified from TGFBI were sequenced.
Eleven patients from 9 families with granular corneal dystrophy (GCD) presented with a wide spectrum of dot or fleck opacities and shared some similar clinical features. Genetic studies revealed an R124H mutation in 5 families and an R555W mutation in 4 families. A patient with GCD type 2 and an R124H mutation showed a marked increase in opacities in the laser-assisted in situ keratomileusis (LASIK) flap interface. Six patients from 3 families with superficial honeycomb opacities had an R555Q mutation. Of the 4 patients from 3 families with variant lattice line opacities, 3 from 2 families had an R124C mutation, whereas 1 from the third family had an A546D mutation. Spontaneous mutations were detected in 2 families: an R124C mutation in 1 family with lattice corneal dystrophy (LCD) type I and an A546D mutation in the other with atypical LCD.
In most cases, TGFBI-linked corneal dystrophies had good phenotype-genotype correlations; however, some phenotypic variation was present. The most common mutations in Taiwan were R124H in GCD type 2 and R555W in GCD type 1. The R555Q mutation in Thiel-Behnke corneal dystrophy is not as rare in Taiwan as it is in other Asian countries. Sequencing of TGFBI can aid in the precise classification of these corneal dystrophies.
在台湾大学附属医院确定与人类转化生长因子-β诱导（TGFBI）突变相关的角膜营养不良患者的表型-基因型相关性。
招募了来自15个家庭的25名患有角膜营养不良的患者。他们接受了裂隙灯显微镜检查和视力检查。从他们的外周血中提取基因组DNA，并对从TGFBI扩增的外显子进行测序。
来自9个颗粒状角膜营养不良（GCD）家庭的11名患者表现出广泛的点状或斑点状混浊，并具有一些相似的临床特征。基因研究显示，5个家庭存在R124H突变，4个家庭存在R555W突变。一名患有2型GCD且有R124H突变的患者在准分子激光原位角膜磨镶术（LASIK）瓣界面处的混浊明显增加。来自3个浅表蜂窝状混浊家庭的6名患者有R555Q突变。在3个具有变异格子状混浊的家庭的4名患者中，2个家庭的3名患者有R124C突变，而第三个家庭的1名患者有A546D突变。在2个家庭中检测到自发突变：1个患有I型格子状角膜营养不良（LCD）的家庭有R124C突变，另一个患有非典型LCD的家庭有A546D突变。
在大多数情况下，与TGFBI相关的角膜营养不良具有良好的表型-基因型相关性；然而，存在一些表型变异。台湾最常见的突变是2型GCD中的R124H和1型GCD中的R555W。蒂尔-贝恩克角膜营养不良中的R555Q突变在台湾并不像在其他亚洲国家那样罕见。TGFBI测序有助于这些角膜营养不良的精确分类。
