一个Reis-Bucklers角膜营养不良遗传家系的表型分析

目的 分析与转化生长因子-β（transforming growth factor-β，TGF-β） 基因突变相关的Reis-Bucklers 角膜营养不良（Reis-Bucklers dystrophy，RBCD） 家系的临床表型特征。 方法 于2013 年7 月将海南省三亚市同一家系17 例成员（患者9 例，正常8 例） 纳入本研究。所有成员进行完整的眼科检查，包括视力、眼压、眼前节裂隙灯检查、眼底检查、角膜敏感度检查和泪液分泌检查，并对临床表型资料进行分析。TGF-β 基因的所有外显子（1 ～ 16 号外显子） 应用聚合酶链反应和直接测序法鉴定TGF-β 基因突变。 结果 该家系患者9 例（ 其中男性6 例，女性3 例） 诊断为Reis-Bucklers 角膜营养不良，发病年龄1 ～ 10（3.67±0.90） 岁，首发症状包括畏光流泪，眼睛疼痛。视力下降年龄6 ～ 13 （8.00±0.78） 岁。此家系中的个体患者角膜营养不良的临床表现有明显差异，主要表现有角膜上皮地图样缺损、浅基质层孤岛样变性混浊、角膜表面铁锈样色素沉积和深部角膜基质层水肿。所有患者角膜敏感度都有减弱甚至消失。 结论 在本研究家系中，TGF-β 基因c.418G ＞ T（p.R124L） 突变引起的患者角膜营养不良存在表型异质性，包括角膜上皮地图样缺损，角膜表面糜烂造成的局部隆起和混浊，角膜表面斑片状棕褐色似铁锈样色素沉积，以及水肿累及全基质层等。

Phenotypes of a family with inheritory Reis-Bucklers corneal dystrophy

Objective To analyze the clinical features of genotypes in a family with Reis-Bucklers corneal dystrophy （RBCD） associated with mutations in human transforming growth factor- β （TGF- β ） gene. Methods Seventeen members of a family （9 patients and 8 normal subjects） in Sanya City, Hainan Province, China, were recruited in this study in July 2013. They underwent visual acuity test, intraocular pressure measurement, corneal sensitivity test, anterior segment slit lamp examination, fundus examination, and tear secretion examination. Their clinical phenotype data were analyzed. Exons 1-16 in TGF- β gene were detected by PCR and mutations in TGF- β gene were identified by direct sequencing. Results Nine patients （6 males and 3 females） in the family were diagnosed with RBCD which occurred at the age of 1-10 years （3.67 ± 0.90 years）. The initial symptoms of RBCD were photophobia and ophthalmalgia. The visual acuity began to reduce in patients at the age of 6-13 years （8.00 ± 0.78 years）. The RBCD was manifested as map-like defect of corneal epithelium, isolated island-like degeneration opacity of superficial stroma, rust-like pigmentation in superficial cornea, edema in deeper corneal stroma, weakened or disappeared cornea sensitivity. Conclusion The mutation p. R124L （c. 418G 〉 T） in TGF- β gene can cause phenotype heterogeneity in RBCD patients, including map-like defect of corneal epithelium, local projection and opacity due to superficial erosion of cornea, rust-like pigmentation in superficial cornea, and edema involving the whole corneal stroma.