Identification of the First De Novo UBIAD1 Gene Mutation Associated with Schnyder Corneal Dystrophy.
Identification of the First De Novo UBIAD1 Gene Mutation Associated with Schnyder Corneal Dystrophy.
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DOI：
10.1155/2016/1968493
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发表时间：
2016
影响因子：
1.9
通讯作者：
Aldave AJ
中科院分区：
文献类型：
--
作者：
Lin BR;Frausto RF;Vo RC;Chiu SY;Chen JL;Aldave AJ
目的.报告在施奈德角膜营养不良（SCD）患者中发现的第一个新生UBIAD 1错义突变。方法.裂隙灯检查进行了一个47岁的妇女没有家族史角膜疾病。先证者的父母，两个姐妹篇和儿子也进行了检查，并收集了所有六个人的基因组DNA。采用桑格测序法筛选UBIAD 1的外显子和外显子-内含子边界。在200条对照染色体中筛选鉴定的突变。计算机模拟分析预测了已鉴定突变对蛋白质功能和结构的影响。结果先证者裂隙灯检查结果与SCD一致。家庭成员的角膜似乎未受影响。在先证者中筛查UBIAD 1发现了一种新的杂合c.308C>T突变，预测其编码错义氨基酸取代p。（Thr103Ile）。这种突变在任何家族成员或200条对照染色体中都没有发现，预计会损害正常的蛋白质功能和结构。结论.我们提出了一种新的杂合从头错义突变UBIAD 1，p。（Thr 103 Ile），在具有SCD的典型临床特征的患者中鉴定。这突出了基因检测在临床诊断环境中的价值，即使在没有阳性家族史的情况下。
Purpose. To report the identification of the first de novo UBIAD1 missense mutation in an individual with Schnyder corneal dystrophy (SCD). Methods. A slit lamp examination was performed on a 47-year-old woman without a family history of corneal disorders. The proband's parents, two sisters, and son were also examined and genomic DNA from all six individuals was collected. The exons and exon-intron boundaries of UBIAD1 were screened using Sanger sequencing. Identified mutations were screened for in 200 control chromosomes. In silico analysis predicted the impact of identified mutations on protein function and structure. Results. Slit lamp examination of the proband revealed findings consistent with SCD. Corneas of the family members appeared unaffected. Screening of UBIAD1 in the proband identified a novel heterozygous c.308C>T mutation, predicted to encode the missense amino acid substitution p.(Thr103Ile). This mutation was not identified in any of the family members or in 200 control chromosomes and was predicted to be damaging to normal protein function and structure. Conclusions. We present a novel heterozygous de novo missense mutation in UBIAD1, p.(Thr103Ile), identified in a patient with classic clinical features of SCD. This highlights the value of genetic testing in clinical diagnostic settings, even in the absence of a positive family history.