Novel Compound Heterozygous Variations in MPDZ Gene Caused Isolated Bilateral Macular Coloboma in a Chinese Family.
Novel Compound Heterozygous Variations in MPDZ Gene Caused Isolated Bilateral Macular Coloboma in a Chinese Family.
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黄斑缺损是一种罕见的先天性视网膜脉络膜缺损，以黄斑区大小不等的病变为特征。先天性MC的病理机制尚不清楚。通过全外显子组分析，在一个中国人孤立性双侧黄斑缺损家系的先证者中发现了多PDZ结构域（MPDZ）蛋白中新的复合杂合变异c.4301delA（p.Asp1434fs*3）和c.5255C>G（p.Ser1752Ter）。分离分析表明，每个未受影响的父母是杂合的两个变种之一。计算机模拟和生物信息学分析的结果与实验数据一致。MPDZ在斑马鱼中的敲除引起椭圆体区的减少、外界膜的破坏以及随后的RPE变性。总的来说，斑马鱼MPDZ的缺失导致视网膜发育失败。这些结果表明，MPDZ在黄斑的发生和维持中起着至关重要的作用，新的复合杂合变异是该中国家庭中常染色体隐性黄斑缺陷症的原因。
Macular coloboma (MC) is a rare congenital retinochoroidal defect characterized by lesions of different sizes in the macular region. The pathological mechanism underlying congenital MC is unknown. Novel compound heterozygous variations, c.4301delA (p.Asp1434fs*3) and c.5255C>G (p.Ser1752Ter), in the multiple PDZ domain (MPDZ) proteins were identified via whole-exome analysis on the proband with isolated bilateral macular coloboma in a Chinese family. Segregation analysis revealed that each of the unaffected parents was heterozygous for one of the two variants. The results of the in silico and bioinformatics analysis were aligned with the experimental data. The knockdown of MPDZ in zebrafish caused a decrease in the ellipsoid zone, a destruction of the outer limiting membrane, and the subsequent RPE degeneration. Overall, the loss of MPDZ in zebrafish contributed to retinal development failure. These results indicate that MPDZ plays an essential role in the occurrence and maintenance of the macula, and the novel compound heterozygous variations were responsible for an autosomal recessive macular deficiency in this Chinese family.
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影响因子：
30.8
作者：
Lindeboom, Rik G. H.;Vermeulen, Michiel;Supek, Fran
通讯作者：
Supek, Fran
DOI：
10.1007/978-1-4939-7649-2_25
发表时间：
2018-01-01
期刊：
SCHWANN CELLS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Cunningham, Rebecca L.;Monk, Kelly R.
通讯作者：
Monk, Kelly R.
影响因子：
8.8
作者：
Boehm, Volker;Haberman, Nejc;Gehring, Niels H.
通讯作者：
Gehring, Niels H.
影响因子：
1.2
作者：
Kiratli, H;Tatlipinar, S
通讯作者：
Tatlipinar, S
影响因子：
4.8
作者：
Coyne, CB;Voelker, T;Bergelson, JM
通讯作者：
Bergelson, JM