Identification of a novel missense mutation of MIP in a Chinese family with congenital cataracts by target region capture sequencing.
Identification of a novel missense mutation of MIP in a Chinese family with congenital cataracts by target region capture sequencing.
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DOI：
10.1038/srep40129
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发表时间：
2017-01-06
影响因子：
4.6
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Jiang B;Chen Y;Xu B;Hong N;Liu R;Qi M;Shen L
先天性白内障具有临床多样性和遗传异质性。为了研究一个中国常染色体显性先天性白内障家族三代人的潜在遗传缺陷，我们招募了接受全面眼科检查的家族成员。通过靶区捕获测序，在MIP基因中发现了一个杂合错义突变C . 634g > C （p.G212R）取代。polyphen2和SIFT的预测结果表明，该突变可能破坏MIP的结构和功能。共聚焦显微镜图像显示，与野生型MIP相比，绿色荧光信号的强度显示突变体的信号弱得多。在HeLa细胞中，G212R-MIP表达减少，且几乎只表达细胞质；而WT-MIP则稳定地分布在细胞质中，并出现在膜结构中。Western blot分析表明，突变型MIP的蛋白表达水平与野生型相比显著降低，但野生型和突变型细胞的mRNA表达水平具有可比性。总之，我们的研究为G212R的一种新的MIP突变提供了遗传和功能证据，该突变导致先天性进行性皮质点状点，有或没有Y缝线。
Congenital cataract is both clinically diverse and genetically heterogeneous. To investigate the underlying genetic defect in three-generations of a Chinese family with autosomal dominant congenital cataracts, we recruited family members who underwent comprehensive ophthalmic examinations. A heterozygous missense mutation c.634G > C (p.G212R) substitution was identified in the MIP gene through target region capture sequencing. The prediction results of PolyPhen-2 and SIFT indicated that this mutation was likely to damage the structure and function of MIP. Confocal microscopy images showed that the intensity of the green fluorescent signal revealed much weaker signal from the mutant compared to the wild-type MIP. The expressed G212R-MIP was diminished and almost exclusively cytoplasmic in the HeLa cells; whereas the WT-MIP was stable dispersed throughout the cytoplasm, and it appeared to be in the membrane structure. Western blot analysis indicated that the protein expression level of the mutant form of MIP was remarkably reduced compared with that of the wild type, however, the mRNA levels of the wild-type and mutant cells were comparable. In conclusion, our study presented genetic and functional evidence for a novel MIP mutation of G212R, which leads to congenital progressive cortical punctate with or without Y suture.
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影响因子：
13.7
作者：
Haargaard, B;Wohlfahrt, J;Melbye, M
通讯作者：
Melbye, M
影响因子：
16.8
作者：
Buck, Teresa M.;Wagner, Justin;Skach, William R.
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
RAHI, JS;SRIPATHI, S;FOSTER, A
通讯作者：
FOSTER, A
DOI：
10.1002/ar.a.10080
发表时间：
2003-08-01
期刊：
ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY
影响因子：
--
作者：
Al-Ghoul, KJ;Kirk, T;Kuszak, JR
通讯作者：
Kuszak, JR