Identification of a Heterozygous Mutation in the TGFBI Gene in a Hui-Chinese Family with Corneal Dystrophy
Identification of a Heterozygous Mutation in the TGFBI Gene in a Hui-Chinese Family with Corneal Dystrophy
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一个回族角膜营养不良家系TGFBI基因杂合突变的鉴定
DOI：
10.1155/2019/2824179
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发表时间：
2019-01-01
影响因子：
1.9
通讯作者：
Deng, Hao
中科院分区：
文献类型：
--
作者：
Xiang, Qin;Yuan, Lamei;Deng, Hao
背景/目标。角膜营养不良（Cornealdystrophies，CD）是一组遗传性异质性角膜疾病，其由于在角膜不同层中沉积物的进行性积累而导致视力损害。到目前为止，几个基因的突变已经导致了各种CD。本研究的目的是确定一个三代回族家族中与颗粒状角膜营养不良I型（GCD 1）相关的基因突变。方法.本研究招募了一个三代回族GCD 1家系。裂隙灯生物显微镜，光学相干断层扫描，共聚焦显微镜进行，以确定可用的成员的临床特征。对两名患者进行全外显子组测序，以筛选家族中潜在的致病变异。桑格测序用于检测家族成员中的变异。结果临床检查显示，两名患者的角膜基底上皮层和浅层基质层中存在双侧丰富的多发性灰白色阴影。全外显子组测序结果显示，两例患者均存在转化生长因子β诱导基因（TGFBI）的一个杂合错义突变（c.1663C>T，p.Arg555Trp），桑格测序证实该突变与该家系的遗传易感性共分离。结论.结果提示，该回族家系GCD 1基因突变为TGFBI c.1663C>T（p.Arg555Trp）杂合突变，对该家系的遗传咨询有重要意义。
Background/Aims. Corneal dystrophies (CDs) belong to a group of hereditary heterogeneous corneal diseases which result in visual impairment due to the progressive accumulation of deposits in different corneal layers. So far, mutations in several genes have been responsible for various CDs. The purpose of this study is to identify gene mutations in a three-generation Hui-Chinese family associated with granular corneal dystrophy type I (GCD1). Methods. A three-generation Hui-Chinese pedigree with GCD1 was recruited for this study. Slit-lamp biomicroscopy, optical coherence tomography, and confocal microscopy were performed to determine the clinical features of available members. Whole exome sequencing was performed on two patients to screen for potential disease-causing variants in the family. Sanger sequencing was used to test the variant in the family members. Results. Clinical examinations demonstrated bilaterally abundant multiple grayish-white opacities in the basal epithelial and superficial stroma layers of corneas of the two patients. Whole exome sequencing revealed that a heterozygous missense mutation (c.1663C>T, p.Arg555Trp) in the transforming growth factor beta-induced gene (TGFBI) was shared by the two patients, and it cosegregated with this disease in the family confirmed by Sanger sequencing. Conclusions. The results suggested that the heterozygous TGFBI c.1663C>T (p.Arg555Trp) mutation was responsible for GCD1 in the Hui-Chinese family, which should be of great help in genetic counseling for this family.