Novel mutation (V505D) of the TGFBI gene found in a Chinese family with lattice corneal dystrophy, type I
Novel mutation (V505D) of the TGFBI gene found in a Chinese family with lattice corneal dystrophy, type I
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DOI：
10.1007/s10384-004-0167-7
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发表时间：
2005-03
影响因子：
2.4
通讯作者：
X. Tian;K. Fujiki;Wei Wang;A. Murakami;P. Xie;A. Kanai;Zuguo Liu
中科院分区：
文献类型：
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作者：
X. Tian;K. Fujiki;Wei Wang;A. Murakami;P. Xie;A. Kanai;Zuguo Liu
目的报告在一个中国 I 型格子状角膜营养不良 (LCDI) 家系中发现的人类转化生长因子 β 诱导 (TGFBI) 基因的新 V505D 突变。方法从中国 LCDI 家系中 8 名受影响和 4 名未受影响成员的外周血白细胞中提取基因组 DNA。通过聚合酶链式反应扩增TGFBI基因的外显子并直接测序。还分析了 50 名中国正常人作为对照。先证者角膜移植术后对角膜纽扣进行组织病理学检查。结果在所有受影响的成员中均检测到TGFBI基因（V505D）外显子11的密码子505处的杂合单碱基对颠换（GTC至GAC，缬氨酸至天冬氨酸）。在未受影响的成员或 50 名正常对照中未发现突变。该突变在三代中与疾病表型共分离。尽管裂隙灯检查在大多数病例中显示出 LCDI 的特征，但症状出现的年龄比具有 R124C 突变的 LCDI 病例晚数年。通过组织病理学检查，在间质中观察到大量淀粉样蛋白沉积，包括鲍曼膜下。结论 TGFBI 基因中的新 V505D 突变导致该中国家庭的 LCDI。这是第四个报道的与 LCDI 相关的 TGFBI 基因突变。
PurposeTo report a novel V505D mutation of the human transforming growth factor beta-induced (TGFBI) gene found in a Chinese family with lattice corneal dystrophy, type I (LCDI).MethodsGenomic DNA was extracted from peripheral leukocytes from eight affected and four unaffected members of a Chinese family with LCDI. Exons of theTGFBIgene were amplified by polymerase chain reaction and directly sequenced. Fifty normal Chinese individuals were also analysed as controls. Histopathological examination of a corneal button was performed after keratoplasty of the proband.ResultsA heterozygous single-base-pair transversion (GTC to GAC, valine to aspartic acid) at codon 505 in exon 11 of theTGFBIgene (V505D) was detected in all of the affected members. No mutation was found in the unaffected members or in the 50 normal controls. The mutation cosegregated with the disease phenotype throughout three generations. Although a slit-lamp examination showed features of LCDI in most cases, the age at onset of the symptoms was several years later than that in cases of LCDI with an R124C mutation. By histopathological examination, numerous amyloid deposits were observed in the stroma, including beneath Bowman’s membrane.ConclusionA novel V505D mutation in theTGFBIgene causes LCDI in this Chinese family. It is the fourth reported mutation of theTGFBIgene associated with LCDI.