Fujiki K, Hotta Y, Nakayasu K, Yamaguchi T, Kato T, Uesugi Y, Ha N T, Endo S, Ishida N, Lu W N, Kanai A
Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
Cornea. 2000 Nov;19(6):842-5. doi: 10.1097/00003226-200011000-00015.
To investigate mutations of the human transforming growth factor beta-induced gene (TGFBI), transforming growth factor-beta-induced gene product (betaig-h3, keratoepithelin), in Japanese patients with Avellino corneal dystrophy (ACD), lattice corneal dystrophy (LCD), granular corneal dystrophy (GCD), and Reis-Bücklers corneal dystrophy (RBCD).
Genomic DNA was extracted from the peripheral blood of 75 patients and 7 unaffected relatives from 60 families with ACD, 34 patients and 8 unaffected relatives from 21 families with LCD, 4 patients and 4 unaffected relatives from 4 families with GCD, and 4 patients and an unaffected relative from 3 families with RBCD. Fifty normal volunteers served as controls. Exons 4, 11, and 12 of the TGFBI gene were amplified by polymerase chain reaction and were directly sequenced.
Six different heterozygous missense mutations were detected in codons R124, L518, L527, and R555 of the TGFBI gene in the 117 patients from 88 families. A R124H mutation was detected in the patients with ACD. A R124C mutation was detected in the patients with LCD type 1 (LCD1), L518P was in atypical LCDI, and L527R in LCD with opacities deep in stroma. A R555W mutation was detected in the patients with GCD. A R555Q mutation was detected in the patients with RBCD.
We conclude that codons R124 and R555 of the TGFBI gene are also hot spots in Japanese patients with ACD, LCD, GCD, and RBCD. Many Japanese patients with CD had ACD with R124H mutation. GCD with R555W mutation was rare.
研究日本阿韦利诺角膜营养不良（ACD）、格子状角膜营养不良（LCD）、颗粒状角膜营养不良（GCD）和赖斯-布克勒角膜营养不良（RBCD）患者中人类转化生长因子β诱导基因（TGFBI），即转化生长因子β诱导基因产物（βig-h3，角膜上皮素）的突变情况。
从60个患有ACD的家庭中的75例患者和7名未受影响的亲属、21个患有LCD的家庭中的34例患者和8名未受影响的亲属、4个患有GCD的家庭中的4例患者和4名未受影响的亲属，以及3个患有RBCD的家庭中的4例患者和1名未受影响的亲属的外周血中提取基因组DNA。50名正常志愿者作为对照。通过聚合酶链反应扩增TGFBI基因的第4、11和12外显子并直接测序。
在来自88个家庭的117例患者中，在TGFBI基因的密码子R124、L518、L527和R555处检测到6种不同的杂合错义突变。在ACD患者中检测到R124H突变。在1型LCD（LCD1）患者中检测到R124C突变，非典型LCDI中检测到L518P突变，基质深层有混浊的LCD中检测到L527R突变。在GCD患者中检测到R555W突变。在RBCD患者中检测到R555Q突变。
我们得出结论，TGFBI基因的密码子R124和R555也是日本ACD、LCD、GCD和RBCD患者的热点突变位点。许多日本角膜营养不良患者患有携带R124H突变的ACD。携带R555W突变的GCD很少见。
