Hao Xiao-Dan, Zhang Yang-Yang, Chen Peng, Li Su-Xia, Wang Ye
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, Shandong Province, China.
Shandong Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences, Jinan 250021, Shandong Province, China.
Int J Ophthalmol. 2016 Feb 18;9(2):198-203. doi: 10.18240/ijo.2016.02.03. eCollection 2016.
To uncover the mutations profile of transforming growth factor beta-induced (TGFBI) gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations.
Forty-two subjects (6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients) of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing.
We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy (GCD) (including 3 families and 8 sporadic patients) and lattice corneal dystrophy (LCD) (including 2 families and 9 sporadic patients). The next phenotypes were corneal dystrophy of Bowman layer (CDB) (1 family and 1 sporadic patient) and epithelial basement membrane dystrophy (EBMD) (1 sporadic patient). Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient.
GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD. Our findings extend the mutational spectrum of TFGBI, and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population.
揭示中国角膜营养不良患者中转化生长因子β诱导（TGFBI）基因的突变谱，并进一步研究基因型-表型相关性特征。
对42名中国受试者（6个无关家族，包括15名患者和8名未患病成员，以及19名单发患者）进行表型和基因型特征分析。通过裂隙灯摄影记录患者的角膜表型。采用直接测序法对TGFBI编码区进行突变筛查。
我们检测到四种角膜营养不良类型。最常见的表型是颗粒状角膜营养不良（GCD）（包括3个家族和8名单发患者）和格子状角膜营养不良（LCD）（包括2个家族和9名单发患者）。其次是Bowman层角膜营养不良（CDB）（1个家族和1名单发患者）和上皮基底膜营养不良（EBMD）（1名单发患者）。在30名角膜营养不良患者中鉴定出6种导致TGFBI角膜营养不良的不同突变。分别是，1个家族和2名单发GCD患者中的p.R124H突变，2个家族和3名单发GCD患者中的p.R555W突变，2个家族和7名单发LCD患者中的p.R124C突变，1名单发LCD患者中的p.A620D突变，1名单发LCD患者中的p.H626R突变，以及1个家族和1名单发CDB患者中的p.R555Q突变。其余3名非典型GCD患者和1名EBMD患者未检测到突变。
GCD和LCD是中国人群中最常见的表型。R555W是GCD最常见的突变；R124C是LCD最常见的突变。我们的研究结果扩展了TFGBI的突变谱，这是在中国人群中广泛描绘的与各种角膜营养不良相关的TGFBI突变谱。
