Li Yin, Li Tuo, Song Xiu-Sheng, Li Jia-Zhang, Wu Qing-Song, Li Hong-Yan
Department of Ophthalmology, Central Hospital of Enshi Autonomous Prefecture, Enshi Autonomous Prefecture 445000, Hubei Province, China.
Int J Ophthalmol. 2012;5(3):301-6. doi: 10.3980/j.issn.2222-3959.2012.03.10. Epub 2012 Jun 18.
To investigate whether mutations in TGFBI gene or CHST6 gene correlated with stromal corneal dystrophies (CD) in 8 Chinese probands.
Eight unrelated patients with stromal corneal dystrophies were recruited in this study; all affected members were assessed by completely ophthalmologic examinations. Genomic DNA was extracted from peripheral leukocytes, 17 exons of TGFBI gene and the exon of CHST6 gene were amplified by polymerase chain reaction (PCR), sequenced directly and compared with the reference database.
Three heterozygous mutations in TGFBI gene were identified in six patients: c. 370C>T (p.Arg124Cys) was found in exon 4 of TGFBI gene in three members, c. 371G>A (p.Arg124His) was found in one patient; c. 1663C>T (p.Arg555Trp) was found in exon 12 in other two members. In addition, four polymorphisms with the nucleotide changes rs1442, rs1054124, rs4669, and rs35151677 were found in TGFBI gene. Mutations were not identified in the rest of 2 affected individuals in TGFBI gene or CHST6 gene.
Within these patients, R124C, R124H and R555W mutations were co-segregated with the disease phenotypes and were specific mutations for lattice corneal dystrophy type I (LCD I), Avellino corneal dystrophy (ACD, GCD II), granular corneal dystrophy type I (GCD I), respectively. Our study highlights the prevalence of codon 124 and codon 555 mutations in the TGFBI gene among the Chinese stromal corneal dystrophies patients.
研究转化生长因子β诱导蛋白（TGFBI）基因或碳水化合物硫酸转移酶6（CHST6）基因的突变是否与8例中国先证者的角膜基质营养不良（CD）相关。
本研究招募了8例无关的角膜基质营养不良患者；所有受累成员均接受了全面的眼科检查。从外周血白细胞中提取基因组DNA，通过聚合酶链反应（PCR）扩增TGFBI基因的17个外显子和CHST6基因的外显子，直接测序并与参考数据库进行比较。
在6例患者中鉴定出TGFBI基因的3个杂合突变：3名成员的TGFBI基因第4外显子中发现c.370C>T（p.Arg124Cys），1例患者中发现c.371G>A（p.Arg124His）；另外2名成员的第12外显子中发现c.1663C>T（p.Arg555Trp）。此外，在TGFBI基因中发现了4个核苷酸变化为rs1442、rs1054124、rs4669和rs35151677的多态性。在其余2例受累个体的TGFBI基因或CHST6基因中未发现突变。
在这些患者中，R124C、R124H和R555W突变与疾病表型共分离，分别是I型格子状角膜营养不良（LCD I）、阿韦利诺角膜营养不良（ACD，GCD II）、I型颗粒状角膜营养不良（GCD I）的特异性突变。我们的研究突出了中国角膜基质营养不良患者中TGFBI基因第124密码子和第555密码子突变的普遍性。
