Romero Pablo, Moraga Mauricio, Herrera Luisa
Depto. de Oftalmología, Hospital Clínico José Joaquín Aguirre, Universidad de Chile, Santiago, Chile.
Mol Vis. 2010 Aug 13;16:1601-9.
To describe clinical data and to characterize mutations in the transforming growth factor beta-induced (TGFBI) gene in patients from three unrelated Chilean families with lattice corneal dystrophy type I (LCDI).
Snellen acuity tests, anterior segment slit lamp examinations, dilated fundus evaluations, and tonometry were performed for seven patients--five females and two males belonging to three unrelated families--affected with lattice corneal dystrophy Type I. Genomic DNA was also extracted from peripheral leukocytes from the seven patients and four healthy relatives. The 417C>T mutation (R124C) was screened using PCR-RFLP for the seven patients and four healthy relatives. Exons 11, 12, 13, and 14 were sequenced in one patient not carrying the mutation in codon 124. Comparison of phenotype to genotype was performed.
The seven patients studied exhibited LCDI in both eyes, most of which were symmetric. Affected individuals demonstrated progression from central subepithelial needlelike deposits and polymorphic anterior stromal opacities. The age at onset of symptoms varied between six to 15 years old in Family One; the patient in Family Two was five years old and the patient in Family Three was 21 years old. Visual acuity varied from 1.0 to 0.05. Two patients, aged 50 and 45 years, underwent penetrating keratoplasty in both eyes, and two patients, aged 47 and 24 years, underwent penetrating keratoplasty in one eye. The only patient in Family Three exhibited a somewhat distinct phenotype, with yellowish discoloration in the anterior stroma and fewer, but thicker lattice lines than the patients in Families One and Two. Screening for the mutation C>T at the nucleotide position 417 (R124C) in exon 4 in the three families revealed the heterozygous R124C mutation in Families One and Two. In Family Two, the mutation was a de novo mutation, as neither parent was a carrier. Screening by sequencing analysis for mutation in exons 11, 12, 13, and 14 in the affected patient in Family Three revealed a heterozygous A1762G mutation (H572R) in exon 13.
This is the second report of the 417C>T mutation and the first report of 1762 A>G mutation (H572R) in Chilean patients. The H572R mutation identified is associated with a distinct lattice corneal dystrophy type I phenotype.
描述来自三个不相关智利家庭的患有I型格子状角膜营养不良（LCDI）患者的临床数据，并鉴定转化生长因子β诱导（TGFBI）基因突变特征。
对来自三个不相关家庭的7例患者（5例女性和2例男性）进行了Snellen视力测试、眼前节裂隙灯检查、散瞳眼底评估和眼压测量，这些患者均患有I型格子状角膜营养不良。还从这7例患者和4名健康亲属的外周血白细胞中提取了基因组DNA。使用PCR-RFLP对7例患者和4名健康亲属进行417C>T突变（R124C）筛查。对1例密码子124未携带突变的患者的第11、12、13和14外显子进行测序。进行了表型与基因型的比较。
所研究的7例患者双眼均表现为I型格子状角膜营养不良，大多数为对称性。受累个体表现为从中央上皮下针状沉积物和多形性前基质混浊进展。在家族一中，症状发作年龄在6至15岁之间；家族二中的患者为5岁，家族三中的患者为21岁。视力从1.0到0.05不等。2例年龄分别为50岁和45岁的患者双眼接受了穿透性角膜移植术，2例年龄分别为47岁和24岁的患者单眼接受了穿透性角膜移植术。家族三中唯一的患者表现出 somewhat distinct 表型，前基质有淡黄色变色，与家族一和家族二中的患者相比，格子线较少但较厚。对三个家族中第4外显子核苷酸位置417处的C>T突变（R124C）进行筛查，发现家族一和家族二中存在杂合性R124C突变。在家族二中，该突变是一个新生突变，因为其父母均不是携带者。对家族三中受影响患者的第11、12、13和14外显子进行测序分析筛查突变，发现第13外显子存在杂合性A1762G突变（H572R）。
这是智利患者中417C>T突变的第二篇报道，也是1762A>G突变（H572R）的第一篇报道。所鉴定的H572R突变与一种独特的I型格子状角膜营养不良表型相关。
