The TGFBI R555W mutation induces a new granular corneal dystrophy type I phenotype
The TGFBI R555W mutation induces a new granular corneal dystrophy type I phenotype
复制标题
TGFBI R555W突变诱导一种新的颗粒性角膜营养不良I型表型
作者：
申屠形超
目的 报告一种不同形式的转化生长因子-β 诱导 (TGFBI) 基因相关角膜营养不良的临床和分子特征，表现出新的 I 型颗粒角膜营养不良 (CDGG1) 表型。方法对发现常染色体显性遗传病的中国家庭的所有个体进行全面的眼科检查。 DNA 是从每个参与受试者的外周血白细胞中获得的。遗传分析包括角蛋白 3 (KRT3)、角蛋白 12 (KRT12) 和 TGFBI 聚合酶链式反应 (PCR) 扩增以及基因组 DNA 外显子的自动核苷酸测序。结果该家系的角膜表型以不同角膜深度的多发性双侧点状圆形混浊为特征，部分受影响个体仅在上皮中出现混浊，这与典型的CDGG1表型不同。 TGFBI 分析显示，所有受影响个体的外显子 12 (c.1663C>T) 均存在杂合点突变，预测存在 p.R555W 错义突变。结论该家系TGFBI R555W突变导致的表型与CDGG1典型病例不同。我们建议这种疾病应归类为 CDGG1 的新表型，这一发现证明了基因诊断在角膜营养不良中的重要性。
Purpose To report the clinical and molecular features of a distinct form of transforming growth factor-β-induced (TGFBI) gene-linked corneal dystrophy exhibiting a new granular corneal dystrophy type I (CDGG1) phenotype. Methods A complete ophthalmologic examination was performed in all individuals of a Chinese family in which autosomal dominant transmission of the disease had been observed. DNA was obtained from the peripheral blood leukocytes of each participating subject. Genetic analyses included keratin 3 (KRT3), keratin 12 (KRT12), and TGFBI polymerase chain reaction (PCR) amplification and automated nucleotide sequencing of exons from the genomic DNA. Results The corneal phenotype in this pedigree was characterized by multiple bilateral dot-like, circular opacities at different corneal depths, with some of the affected individuals only having opacities in the epithelium, which is different from the typical CDGG1 phenotype. TGFBI analysis revealed a heterozygous point mutation at exon 12 (c.1663C>T) in all of the affected individuals, predicting a p.R555W missense mutation. Conclusions The phenotype which resulted from the TGFBI R555W mutation in this family is distinct from that observed in the typical case of CDGG1. We propose this disorder should be classified as a new phenotype of CDGG1, and this finding demonstrates the importance of gene diagnosis in the corneal dystrophies.
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DOI：
10.1016/s0084-392x(08)79083-x
发表时间：
2008
期刊：
Yearbook of Ophthalmology
影响因子：
--
作者：
K. Hammersmith
通讯作者：
K. Hammersmith
影响因子：
3.7
作者：
A. Bron
通讯作者：
A. Bron
影响因子：
11.6
作者：
R. Quatrano
通讯作者：
R. Quatrano
影响因子：
30.8
作者：
Munier, FL;Korvatska, E;Schorderet, DF
通讯作者：
Schorderet, DF
影响因子：
3.9
作者：
Kannabiran, Chitra;Klintworth, Gordon K.
通讯作者：
Klintworth, Gordon K.