Nakatsukasa Mina, Kawasaki Satoshi, Yamasaki Kenta, Fukuoka Hideki, Matsuda Akira, Nishida Kohji, Kinoshita Shigeru
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Mol Vis. 2011 Apr 19;17:965-70.
To report two novel mutation of the tumor-associated calcium signal transducer 2 (TACSTD2) gene in 3 Japanese patients with gelatinous drop-like corneal dystrophy (GDLD).
Genomic DNAs were extracted from the peripheral blood of 3 Japanese families. The coding region of TACSTD2 was amplified by polymerase chain reaction (PCR) and subjected to direct sequencing analysis. Plasmid vectors harboring normal and mutated TACSTD2 were transfected to the immortalized human corneal epithelial cells to identify the subcellular localization of the normal and mutated TACSTD2 gene products.
Sequencing analysis of TACSTD2 revealed two novel homozygous mutations (c.840_841insTCATCATCGCCGGCCTCATC and c.675C>A which may result in frameshift (p.Ile281SerfsX23) and nonsense (p.Tyr225X) mutations, respectively) in the 3 GDLD patients. Protein expression analysis showed that the mutated gene product was distributed diffusely in the cytoplasm, whereas the normal gene product accumulated at the cell-to-cell borders.
This study reports two novel mutations in 3 GDLD families and expands the spectrum of mutations in TACSTD2 that may cause pathological corneal amyloidosis.
报告3例日本凝胶状滴状角膜营养不良（GDLD）患者肿瘤相关钙信号转导蛋白2（TACSTD2）基因的两种新突变。
从3个日本家庭的外周血中提取基因组DNA。通过聚合酶链反应（PCR）扩增TACSTD2的编码区，并进行直接测序分析。将携带正常和突变TACSTD2的质粒载体转染至永生化人角膜上皮细胞，以确定正常和突变TACSTD2基因产物的亚细胞定位。
TACSTD2的测序分析在3例GDLD患者中发现了两种新的纯合突变（c.840_841insTCATCATCGCCGGCCTCATC和c.675C>A，分别可能导致移码突变（p.Ile281SerfsX23）和无义突变（p.Tyr225X））。蛋白质表达分析表明，突变的基因产物在细胞质中呈弥漫性分布，而正常基因产物则聚集在细胞间边界处。
本研究报告了3个GDLD家系中的两种新突变，并扩大了可能导致病理性角膜淀粉样变性的TACSTD2基因突变谱。
